Diana Mahoney

HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.

“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the 19-center NCCN.

Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.

Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.

In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.

The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.

And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not. It has been hypothesized that the antineoplastic effects of low-molecular-weight heparins may alter the natural history of malignant disease, he noted.

Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis, Dr. Jahanzeb reported.

“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.

It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.

HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.

“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the 19-center NCCN.

Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.

Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.

In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.

The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.

And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not. It has been hypothesized that the antineoplastic effects of low-molecular-weight heparins may alter the natural history of malignant disease, he noted.

Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis, Dr. Jahanzeb reported.

“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.

It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.

HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.

“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the 19-center NCCN.

Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.

Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.

In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.

The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.

And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not. It has been hypothesized that the antineoplastic effects of low-molecular-weight heparins may alter the natural history of malignant disease, he noted.

Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis, Dr. Jahanzeb reported.

“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.

It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.

HOLLYWOOD, FLA. — An aromatase inhibitor, either alone or after tamoxifen therapy, is better than tamoxifen alone for the long-term prevention of breast cancer in postmenopausal women with invasive breast cancer, according to updated treatment guidelines from the National Comprehensive Cancer Network.

Several recent clinical trials have shown that adjuvant endocrine therapy with the aromatase inhibitors anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) can significantly improve disease-free survival in postmenopausal women, compared with tamoxifen as a single agent.

Consequently, “tamoxifen alone [in this patient population] has fallen off the radar screen,” said Robert Carlson, M.D., chair of the NCCN panel that revised the guidelines, which were last updated in 2004. The network's 19 member institutions are designated as comprehensive cancer centers by the National Cancer Institute.

The updated guidelines recommend that women who are postmenopausal when they begin adjuvant therapy receive one of the following treatment regimens:

▸ Anastrozole for 5 years.

▸ Tamoxifen for 2-3 years, followed by exemestane or anastrozole to complete 5 years of therapy.

▸ Tamoxifen for 4.5-6 years, followed by letrozole for 5 years.

▸ Tamoxifen for 5 years for women with contraindications for, or who decline, aromatase inhibitors.

The new recommendations are based primarily on findings from three randomized controlled studies of aromatase inhibitors in postmenopausal women, he said at the annual conference of the NCCN.

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared anastrozole, alone or used with tamoxifen, with tamoxifen alone as 5-year adjuvant treatment for women with early breast cancer following primary treatment with surgery, radiotherapy, and/or chemotherapy. The combination arm was stopped following initial analysis showing it to have similar efficacy to the tamoxifen alone arm.

The ATAC cohort included approximately 9,300 breast cancer patients who had good prognoses: 61% had lymph-node negative disease and 64% had tumors smaller than 2 cm in diameter.

The most recent analysis of the ATAC data, representing a median 68 months of follow-up, showed significant improvements in disease-free survival, recurrence-free survival, and distant disease-free survival in those receiving anastrozole.

“Anastrozole prevents one in four of the relapses experienced by patients on tamoxifen,” said Dr. Carlson of Stanford (Calif.) University. The anastrozole patients also had fewer diagnoses of endometrial cancer, thromboembolic and cerebrovascular events, and hot flashes. Women with hormone-receptor-positive disease benefitted the most from adjuvant therapy with anastrozole.

Another study, the MA-17 trial coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queen's University, Kingston, Ont., compared the outcomes of nearly 5,200 women whose adjuvant therapy included 5 years of tamoxifen followed by 5 years of letrozole or placebo. At the median 2.5-year follow-up, patients in the letrozole group had a 40% overall reduction in their risk of metastases, compared with those in the tamoxifen/placebo group.

In the Intergroup Exemestane Study (IES) of more than 4,700 women with estrogen-receptor-positive breast cancer, patients who switched to exemestane after 2 or 3 years of taking tamoxifen for the remainder of 5 years total treatment experienced a 32% reduction in the risk of recurrence of the disease at 3 years, compared with those continuing tamoxifen for 5 years. The exemestane group had fewer local and distant tumors as well as a reduced incidence of new cancer in the other breast.

Because the three selective aromatase inhibitors appear to have similar antitumor efficacy and toxicity profiles, the revised guidelines do not recommend one regimen over another. “The optimal use of these [aromatase inhibitors] as adjuvant therapy, either instead of or sequenced with tamoxifen, has yet to be determined through ongoing trials,” Dr. Carlson said.

When making treatment decisions, physicians should try to gauge how well the patient fits the criteria of the clinical trials on which the recommendations are based and use the regimen that most closely approximates the clinical situation, he advised.

The guidelines for adjuvant hormonal therapy in premenopausal women have been updated as well, Dr. Carlson reported. Women who are premenopausal when adjuvant hormonal therapy is initiated should receive 2-3 years of treatment with tamoxifen with or without ovarian supplementation or ablation.

After this round of treatment, women who continue to be premenopausal should complete 5 years of tamoxifen therapy, Dr. Carlson said. “If, after the first round of adjuvant therapy with tamoxifen, a woman becomes postmenopausal, she should complete the 5 years of tamoxifen, followed by 5 years of letrozole because of the success of this regimen in postmenopausal women,” he said.

Because the ovarian function of some women who appear to become postmenopausal while on tamoxifen resumes when the drug is discontinued and treatment with an aromatase inhibitor begins, serial monitoring of plasma estradiol and FSH levels should be ongoing. “If ovarian function resumes, the aromatase inhibitor should be discontinued and tamoxifen therapy reinitiated,” Dr. Carlson said.

Guidelines Define Menopause

Critical to the appropriate clinical application of the updated NCCN breast cancer treatment recommendations is a standardized definition of menopause.

“You wouldn't think a definition of menopause would be needed, but just about all studies that have been done in postmenopausal women define [menopause] differently,” Dr. Carlson said. This can cause problems and confusion, particularly with respect to treatment with aromatase inhibitors, which are most effective in postmenopausal women.

Menopause is generally the permanent cessation of menses. “As the term is used in breast cancer management, it includes a profound and permanent decrease in ovarian estrogen synthesis,” the revised guidelines state. Reasonable criteria for determining menopause include any of the following:

▸ Prior bilateral oophorectomy.

▸ Age 60 years or older.

▸ Age younger than 60 years and amenorrheic for at least 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression, and FSH and estradiol in the postmenopausal range.

▸ Age younger than 60 years and FSH and plasma estradiol levels in postmenopausal range in women taking tamoxifen or toremifene.

It is not possible to assign menopausal status to women receiving an LHRH agonist or antagonist, the guidelines state. Amenorrhea is not a reliable indicator of menopausal status in women who are premenopausal at the outset of adjuvant chemotherapy.

“Women who undergo chemotherapy treatments that permanently stop menses may still produce estradiol at levels that are premenopausal,”commented Dr. Carlson, stressing that premenopausal estrogen levels can influence treatment with aromatase inhibitors.

HOLLYWOOD, FLA. — An aromatase inhibitor, either alone or after tamoxifen therapy, is better than tamoxifen alone for the long-term prevention of breast cancer in postmenopausal women with invasive breast cancer, according to updated treatment guidelines from the National Comprehensive Cancer Network.

Several recent clinical trials have shown that adjuvant endocrine therapy with the aromatase inhibitors anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) can significantly improve disease-free survival in postmenopausal women, compared with tamoxifen as a single agent.

Consequently, “tamoxifen alone [in this patient population] has fallen off the radar screen,” said Robert Carlson, M.D., chair of the NCCN panel that revised the guidelines, which were last updated in 2004. The network's 19 member institutions are designated as comprehensive cancer centers by the National Cancer Institute.

The updated guidelines recommend that women who are postmenopausal when they begin adjuvant therapy receive one of the following treatment regimens:

▸ Anastrozole for 5 years.

▸ Tamoxifen for 2-3 years, followed by exemestane or anastrozole to complete 5 years of therapy.

▸ Tamoxifen for 4.5-6 years, followed by letrozole for 5 years.

▸ Tamoxifen for 5 years for women with contraindications for, or who decline, aromatase inhibitors.

The new recommendations are based primarily on findings from three randomized controlled studies of aromatase inhibitors in postmenopausal women, he said at the annual conference of the NCCN.

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared anastrozole, alone or used with tamoxifen, with tamoxifen alone as 5-year adjuvant treatment for women with early breast cancer following primary treatment with surgery, radiotherapy, and/or chemotherapy. The combination arm was stopped following initial analysis showing it to have similar efficacy to the tamoxifen alone arm.

The ATAC cohort included approximately 9,300 breast cancer patients who had good prognoses: 61% had lymph-node negative disease and 64% had tumors smaller than 2 cm in diameter.

The most recent analysis of the ATAC data, representing a median 68 months of follow-up, showed significant improvements in disease-free survival, recurrence-free survival, and distant disease-free survival in those receiving anastrozole.

“Anastrozole prevents one in four of the relapses experienced by patients on tamoxifen,” said Dr. Carlson of Stanford (Calif.) University. The anastrozole patients also had fewer diagnoses of endometrial cancer, thromboembolic and cerebrovascular events, and hot flashes. Women with hormone-receptor-positive disease benefitted the most from adjuvant therapy with anastrozole.

Another study, the MA-17 trial coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queen's University, Kingston, Ont., compared the outcomes of nearly 5,200 women whose adjuvant therapy included 5 years of tamoxifen followed by 5 years of letrozole or placebo. At the median 2.5-year follow-up, patients in the letrozole group had a 40% overall reduction in their risk of metastases, compared with those in the tamoxifen/placebo group.

In the Intergroup Exemestane Study (IES) of more than 4,700 women with estrogen-receptor-positive breast cancer, patients who switched to exemestane after 2 or 3 years of taking tamoxifen for the remainder of 5 years total treatment experienced a 32% reduction in the risk of recurrence of the disease at 3 years, compared with those continuing tamoxifen for 5 years. The exemestane group had fewer local and distant tumors as well as a reduced incidence of new cancer in the other breast.

Because the three selective aromatase inhibitors appear to have similar antitumor efficacy and toxicity profiles, the revised guidelines do not recommend one regimen over another. “The optimal use of these [aromatase inhibitors] as adjuvant therapy, either instead of or sequenced with tamoxifen, has yet to be determined through ongoing trials,” Dr. Carlson said.

When making treatment decisions, physicians should try to gauge how well the patient fits the criteria of the clinical trials on which the recommendations are based and use the regimen that most closely approximates the clinical situation, he advised.

The guidelines for adjuvant hormonal therapy in premenopausal women have been updated as well, Dr. Carlson reported. Women who are premenopausal when adjuvant hormonal therapy is initiated should receive 2-3 years of treatment with tamoxifen with or without ovarian supplementation or ablation.

After this round of treatment, women who continue to be premenopausal should complete 5 years of tamoxifen therapy, Dr. Carlson said. “If, after the first round of adjuvant therapy with tamoxifen, a woman becomes postmenopausal, she should complete the 5 years of tamoxifen, followed by 5 years of letrozole because of the success of this regimen in postmenopausal women,” he said.

Because the ovarian function of some women who appear to become postmenopausal while on tamoxifen resumes when the drug is discontinued and treatment with an aromatase inhibitor begins, serial monitoring of plasma estradiol and FSH levels should be ongoing. “If ovarian function resumes, the aromatase inhibitor should be discontinued and tamoxifen therapy reinitiated,” Dr. Carlson said.

Guidelines Define Menopause

Critical to the appropriate clinical application of the updated NCCN breast cancer treatment recommendations is a standardized definition of menopause.

“You wouldn't think a definition of menopause would be needed, but just about all studies that have been done in postmenopausal women define [menopause] differently,” Dr. Carlson said. This can cause problems and confusion, particularly with respect to treatment with aromatase inhibitors, which are most effective in postmenopausal women.

Menopause is generally the permanent cessation of menses. “As the term is used in breast cancer management, it includes a profound and permanent decrease in ovarian estrogen synthesis,” the revised guidelines state. Reasonable criteria for determining menopause include any of the following:

▸ Prior bilateral oophorectomy.

▸ Age 60 years or older.

▸ Age younger than 60 years and amenorrheic for at least 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression, and FSH and estradiol in the postmenopausal range.

▸ Age younger than 60 years and FSH and plasma estradiol levels in postmenopausal range in women taking tamoxifen or toremifene.

It is not possible to assign menopausal status to women receiving an LHRH agonist or antagonist, the guidelines state. Amenorrhea is not a reliable indicator of menopausal status in women who are premenopausal at the outset of adjuvant chemotherapy.

“Women who undergo chemotherapy treatments that permanently stop menses may still produce estradiol at levels that are premenopausal,”commented Dr. Carlson, stressing that premenopausal estrogen levels can influence treatment with aromatase inhibitors.

HOLLYWOOD, FLA. — An aromatase inhibitor, either alone or after tamoxifen therapy, is better than tamoxifen alone for the long-term prevention of breast cancer in postmenopausal women with invasive breast cancer, according to updated treatment guidelines from the National Comprehensive Cancer Network.

Several recent clinical trials have shown that adjuvant endocrine therapy with the aromatase inhibitors anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) can significantly improve disease-free survival in postmenopausal women, compared with tamoxifen as a single agent.

Consequently, “tamoxifen alone [in this patient population] has fallen off the radar screen,” said Robert Carlson, M.D., chair of the NCCN panel that revised the guidelines, which were last updated in 2004. The network's 19 member institutions are designated as comprehensive cancer centers by the National Cancer Institute.

The updated guidelines recommend that women who are postmenopausal when they begin adjuvant therapy receive one of the following treatment regimens:

▸ Anastrozole for 5 years.

▸ Tamoxifen for 2-3 years, followed by exemestane or anastrozole to complete 5 years of therapy.

▸ Tamoxifen for 4.5-6 years, followed by letrozole for 5 years.

▸ Tamoxifen for 5 years for women with contraindications for, or who decline, aromatase inhibitors.

The new recommendations are based primarily on findings from three randomized controlled studies of aromatase inhibitors in postmenopausal women, he said at the annual conference of the NCCN.

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared anastrozole, alone or used with tamoxifen, with tamoxifen alone as 5-year adjuvant treatment for women with early breast cancer following primary treatment with surgery, radiotherapy, and/or chemotherapy. The combination arm was stopped following initial analysis showing it to have similar efficacy to the tamoxifen alone arm.

The ATAC cohort included approximately 9,300 breast cancer patients who had good prognoses: 61% had lymph-node negative disease and 64% had tumors smaller than 2 cm in diameter.

The most recent analysis of the ATAC data, representing a median 68 months of follow-up, showed significant improvements in disease-free survival, recurrence-free survival, and distant disease-free survival in those receiving anastrozole.

“Anastrozole prevents one in four of the relapses experienced by patients on tamoxifen,” said Dr. Carlson of Stanford (Calif.) University. The anastrozole patients also had fewer diagnoses of endometrial cancer, thromboembolic and cerebrovascular events, and hot flashes. Women with hormone-receptor-positive disease benefitted the most from adjuvant therapy with anastrozole.

Another study, the MA-17 trial coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queen's University, Kingston, Ont., compared the outcomes of nearly 5,200 women whose adjuvant therapy included 5 years of tamoxifen followed by 5 years of letrozole or placebo. At the median 2.5-year follow-up, patients in the letrozole group had a 40% overall reduction in their risk of metastases, compared with those in the tamoxifen/placebo group.

In the Intergroup Exemestane Study (IES) of more than 4,700 women with estrogen-receptor-positive breast cancer, patients who switched to exemestane after 2 or 3 years of taking tamoxifen for the remainder of 5 years total treatment experienced a 32% reduction in the risk of recurrence of the disease at 3 years, compared with those continuing tamoxifen for 5 years. The exemestane group had fewer local and distant tumors as well as a reduced incidence of new cancer in the other breast.

Because the three selective aromatase inhibitors appear to have similar antitumor efficacy and toxicity profiles, the revised guidelines do not recommend one regimen over another. “The optimal use of these [aromatase inhibitors] as adjuvant therapy, either instead of or sequenced with tamoxifen, has yet to be determined through ongoing trials,” Dr. Carlson said.

When making treatment decisions, physicians should try to gauge how well the patient fits the criteria of the clinical trials on which the recommendations are based and use the regimen that most closely approximates the clinical situation, he advised.

The guidelines for adjuvant hormonal therapy in premenopausal women have been updated as well, Dr. Carlson reported. Women who are premenopausal when adjuvant hormonal therapy is initiated should receive 2-3 years of treatment with tamoxifen with or without ovarian supplementation or ablation.

After this round of treatment, women who continue to be premenopausal should complete 5 years of tamoxifen therapy, Dr. Carlson said. “If, after the first round of adjuvant therapy with tamoxifen, a woman becomes postmenopausal, she should complete the 5 years of tamoxifen, followed by 5 years of letrozole because of the success of this regimen in postmenopausal women,” he said.

Because the ovarian function of some women who appear to become postmenopausal while on tamoxifen resumes when the drug is discontinued and treatment with an aromatase inhibitor begins, serial monitoring of plasma estradiol and FSH levels should be ongoing. “If ovarian function resumes, the aromatase inhibitor should be discontinued and tamoxifen therapy reinitiated,” Dr. Carlson said.

Guidelines Define Menopause

Critical to the appropriate clinical application of the updated NCCN breast cancer treatment recommendations is a standardized definition of menopause.

“You wouldn't think a definition of menopause would be needed, but just about all studies that have been done in postmenopausal women define [menopause] differently,” Dr. Carlson said. This can cause problems and confusion, particularly with respect to treatment with aromatase inhibitors, which are most effective in postmenopausal women.

Menopause is generally the permanent cessation of menses. “As the term is used in breast cancer management, it includes a profound and permanent decrease in ovarian estrogen synthesis,” the revised guidelines state. Reasonable criteria for determining menopause include any of the following:

▸ Prior bilateral oophorectomy.

▸ Age 60 years or older.

▸ Age younger than 60 years and amenorrheic for at least 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression, and FSH and estradiol in the postmenopausal range.

▸ Age younger than 60 years and FSH and plasma estradiol levels in postmenopausal range in women taking tamoxifen or toremifene.

It is not possible to assign menopausal status to women receiving an LHRH agonist or antagonist, the guidelines state. Amenorrhea is not a reliable indicator of menopausal status in women who are premenopausal at the outset of adjuvant chemotherapy.

“Women who undergo chemotherapy treatments that permanently stop menses may still produce estradiol at levels that are premenopausal,”commented Dr. Carlson, stressing that premenopausal estrogen levels can influence treatment with aromatase inhibitors.

HOLLYWOOD, FLA. — Oral temozolomide should be added to radiotherapy for adults newly diagnosed with glioblastoma multiforme, according to updated guidelines for the management of central nervous system cancers.

Recent studies have shown that including the oral alkylating agent in the management of glioblastoma multiforme results in a clinically meaningful, statistically significant survival benefit with minimal additional toxicity, Steven Brem, M.D., said at the annual conference of the National Comprehensive Cancer Network (NCCN).

The new central nervous system cancer guidelines, issued in March, were developed by the NCCN, which comprises 19 member institutions that have been designated as comprehensive cancer centers by the National Cancer Institute. Last updated in 2004, the guidelines also recommend the use of chemotherapeutic polymer implants following glioblastoma resection, said Dr. Brem, chair of the central nervous system guidelines writing panel.

The inclusion of temozolomide in the updated guidelines comes on the heels of the Food and Drug Administration's (FDA's) March 16 approval of the drug for use in combination with radiotherapy for newly diagnosed glioblastoma, the most common type of primary brain tumor in adults, said Dr. Brem, leader of the neuro-oncology program at H. Lee Moffitt Cancer Center in Tampa, Fla.

Both the FDA approval and NCCN guideline update are based in large part on safety and efficacy data from a phase III study by the European Organisation for Research and Treatment of Cancer (EORTC) in which 573 patients newly diagnosed with glioblastoma were randomized to receive radiotherapy alone or in conjunction with temozolomide (N. Engl. J. Med. 2005;352:987–96). The temozolomide group saw a median survival improvement of 2.5 months—”a significant gain and one that can be built upon,” according to Dr. Brem.

With respect to polymer implants, the guidelines state that BCNU wafers (biodegradable 1,3-bis 2-chloroethyl-1-nitrosourea) should be implanted into the cavity created following glioblastoma resection. As the small white wafers erode, they release the chemotherapy agent carmustine directly to the tumor site over an extended period of time. The FDA approved the wafers for use in patients with newly diagnosed glioblastoma in February 2003 based on results of a series of randomized trials. The NCCN treatment update reflects these results as well as the findings of a 2003 phase III trial out of the University Hospital Eppendorf, Hamburg (Germany), in which 240 patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection, followed by postoperative external beam radiation. The BCNU group had a median survival improvement of 2.3 months and a 28% reduction in death risk. Additionally, time-to-decline and neuroperformance measures were significantly improved, and adverse events were comparable, with the exception of increased risk for cerebrospinal fluid leak and intracranial hypertension in the BCNU group (Neuro-oncol. 2003;5:79–88).

For patients in whom the wafers are not implanted, radiation therapy and treatment with temozolomide should be used, he said.

The updated guidelines also recommend aggressive treatment of metastases to the brain from other cancers. In general, surgery is indicated when there are fewer than four resectable metastatic lesions—depending on such factors as histologic type, location, and neurologic function. This recommendation is based on studies that have associated surgery via various modern techniques—image-guided navigation, functional mapping, awake craniotomy for eloquent area, and minimally invasive microneurosurgery—with a median drop in surgical mortality from 11% to 0%, said Dr. Brem. When there are more than three metastases or when surgery is not indicated, whole-brain radiation therapy—which has a 40%–60% response rate, depending on the tumor—should be used. “Where brain metastases were often viewed as fatal, we now consider them treatable. Where radiation [to the brain] was often perceived as too harmful, we now know that focused radiation can improve median survival time,” he said.

For patients with pain and disability resulting from metastatic spine tumors, the guidelines recommend reconstructive spinal surgery over medical management because the former is associated with better quality of life outcomes, said Dr. Brem.

The guidelines also outline the use of imaging as an accurate biomarker for monitoring central nervous system disease progression and recurrence, as well as treatment efficacy, he said.

The updated guidelines are posted atwww.nccn.org/professionals/physician_gls/default.asp

HOLLYWOOD, FLA. — Oral temozolomide should be added to radiotherapy for adults newly diagnosed with glioblastoma multiforme, according to updated guidelines for the management of central nervous system cancers.

Recent studies have shown that including the oral alkylating agent in the management of glioblastoma multiforme results in a clinically meaningful, statistically significant survival benefit with minimal additional toxicity, Steven Brem, M.D., said at the annual conference of the National Comprehensive Cancer Network (NCCN).

The new central nervous system cancer guidelines, issued in March, were developed by the NCCN, which comprises 19 member institutions that have been designated as comprehensive cancer centers by the National Cancer Institute. Last updated in 2004, the guidelines also recommend the use of chemotherapeutic polymer implants following glioblastoma resection, said Dr. Brem, chair of the central nervous system guidelines writing panel.

The inclusion of temozolomide in the updated guidelines comes on the heels of the Food and Drug Administration's (FDA's) March 16 approval of the drug for use in combination with radiotherapy for newly diagnosed glioblastoma, the most common type of primary brain tumor in adults, said Dr. Brem, leader of the neuro-oncology program at H. Lee Moffitt Cancer Center in Tampa, Fla.

Both the FDA approval and NCCN guideline update are based in large part on safety and efficacy data from a phase III study by the European Organisation for Research and Treatment of Cancer (EORTC) in which 573 patients newly diagnosed with glioblastoma were randomized to receive radiotherapy alone or in conjunction with temozolomide (N. Engl. J. Med. 2005;352:987–96). The temozolomide group saw a median survival improvement of 2.5 months—”a significant gain and one that can be built upon,” according to Dr. Brem.

With respect to polymer implants, the guidelines state that BCNU wafers (biodegradable 1,3-bis 2-chloroethyl-1-nitrosourea) should be implanted into the cavity created following glioblastoma resection. As the small white wafers erode, they release the chemotherapy agent carmustine directly to the tumor site over an extended period of time. The FDA approved the wafers for use in patients with newly diagnosed glioblastoma in February 2003 based on results of a series of randomized trials. The NCCN treatment update reflects these results as well as the findings of a 2003 phase III trial out of the University Hospital Eppendorf, Hamburg (Germany), in which 240 patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection, followed by postoperative external beam radiation. The BCNU group had a median survival improvement of 2.3 months and a 28% reduction in death risk. Additionally, time-to-decline and neuroperformance measures were significantly improved, and adverse events were comparable, with the exception of increased risk for cerebrospinal fluid leak and intracranial hypertension in the BCNU group (Neuro-oncol. 2003;5:79–88).

For patients in whom the wafers are not implanted, radiation therapy and treatment with temozolomide should be used, he said.

The updated guidelines also recommend aggressive treatment of metastases to the brain from other cancers. In general, surgery is indicated when there are fewer than four resectable metastatic lesions—depending on such factors as histologic type, location, and neurologic function. This recommendation is based on studies that have associated surgery via various modern techniques—image-guided navigation, functional mapping, awake craniotomy for eloquent area, and minimally invasive microneurosurgery—with a median drop in surgical mortality from 11% to 0%, said Dr. Brem. When there are more than three metastases or when surgery is not indicated, whole-brain radiation therapy—which has a 40%–60% response rate, depending on the tumor—should be used. “Where brain metastases were often viewed as fatal, we now consider them treatable. Where radiation [to the brain] was often perceived as too harmful, we now know that focused radiation can improve median survival time,” he said.

For patients with pain and disability resulting from metastatic spine tumors, the guidelines recommend reconstructive spinal surgery over medical management because the former is associated with better quality of life outcomes, said Dr. Brem.

The guidelines also outline the use of imaging as an accurate biomarker for monitoring central nervous system disease progression and recurrence, as well as treatment efficacy, he said.

The updated guidelines are posted atwww.nccn.org/professionals/physician_gls/default.asp

HOLLYWOOD, FLA. — Oral temozolomide should be added to radiotherapy for adults newly diagnosed with glioblastoma multiforme, according to updated guidelines for the management of central nervous system cancers.

Recent studies have shown that including the oral alkylating agent in the management of glioblastoma multiforme results in a clinically meaningful, statistically significant survival benefit with minimal additional toxicity, Steven Brem, M.D., said at the annual conference of the National Comprehensive Cancer Network (NCCN).

The new central nervous system cancer guidelines, issued in March, were developed by the NCCN, which comprises 19 member institutions that have been designated as comprehensive cancer centers by the National Cancer Institute. Last updated in 2004, the guidelines also recommend the use of chemotherapeutic polymer implants following glioblastoma resection, said Dr. Brem, chair of the central nervous system guidelines writing panel.

The inclusion of temozolomide in the updated guidelines comes on the heels of the Food and Drug Administration's (FDA's) March 16 approval of the drug for use in combination with radiotherapy for newly diagnosed glioblastoma, the most common type of primary brain tumor in adults, said Dr. Brem, leader of the neuro-oncology program at H. Lee Moffitt Cancer Center in Tampa, Fla.

Both the FDA approval and NCCN guideline update are based in large part on safety and efficacy data from a phase III study by the European Organisation for Research and Treatment of Cancer (EORTC) in which 573 patients newly diagnosed with glioblastoma were randomized to receive radiotherapy alone or in conjunction with temozolomide (N. Engl. J. Med. 2005;352:987–96). The temozolomide group saw a median survival improvement of 2.5 months—”a significant gain and one that can be built upon,” according to Dr. Brem.

With respect to polymer implants, the guidelines state that BCNU wafers (biodegradable 1,3-bis 2-chloroethyl-1-nitrosourea) should be implanted into the cavity created following glioblastoma resection. As the small white wafers erode, they release the chemotherapy agent carmustine directly to the tumor site over an extended period of time. The FDA approved the wafers for use in patients with newly diagnosed glioblastoma in February 2003 based on results of a series of randomized trials. The NCCN treatment update reflects these results as well as the findings of a 2003 phase III trial out of the University Hospital Eppendorf, Hamburg (Germany), in which 240 patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection, followed by postoperative external beam radiation. The BCNU group had a median survival improvement of 2.3 months and a 28% reduction in death risk. Additionally, time-to-decline and neuroperformance measures were significantly improved, and adverse events were comparable, with the exception of increased risk for cerebrospinal fluid leak and intracranial hypertension in the BCNU group (Neuro-oncol. 2003;5:79–88).

For patients in whom the wafers are not implanted, radiation therapy and treatment with temozolomide should be used, he said.

The updated guidelines also recommend aggressive treatment of metastases to the brain from other cancers. In general, surgery is indicated when there are fewer than four resectable metastatic lesions—depending on such factors as histologic type, location, and neurologic function. This recommendation is based on studies that have associated surgery via various modern techniques—image-guided navigation, functional mapping, awake craniotomy for eloquent area, and minimally invasive microneurosurgery—with a median drop in surgical mortality from 11% to 0%, said Dr. Brem. When there are more than three metastases or when surgery is not indicated, whole-brain radiation therapy—which has a 40%–60% response rate, depending on the tumor—should be used. “Where brain metastases were often viewed as fatal, we now consider them treatable. Where radiation [to the brain] was often perceived as too harmful, we now know that focused radiation can improve median survival time,” he said.

For patients with pain and disability resulting from metastatic spine tumors, the guidelines recommend reconstructive spinal surgery over medical management because the former is associated with better quality of life outcomes, said Dr. Brem.

The guidelines also outline the use of imaging as an accurate biomarker for monitoring central nervous system disease progression and recurrence, as well as treatment efficacy, he said.

The updated guidelines are posted atwww.nccn.org/professionals/physician_gls/default.asp

BOSTON — Having asthma can make adolescent patients feel different from their peers, “and there is nothing worse to an adolescent than feeling different,” according to Alysa Brimer, a medical student at the University of Missouri, Kansas City.

In addition to the negative social consequences of asthma—including lack of participation in school-based clubs, athletics, and social events—this negative self-perception may decrease patients' compliance with their medication regimens.

Creating social clubs and group athletic activities exclusively for asthmatic youths may go a long way toward mitigating patients' damaged self-esteem and increasing the likelihood of treatment compliance, Ms. Brimer said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Ms. Brimer and colleagues at Children's Mercy Hospital in Kansas City, Missouri, investigated the factors that make asthmatic youths feel different from their healthy friends, and hypothesized that groups made up of asthmatic peers might improve their self-perception.

The investigators reviewed data from an ongoing survey of children with asthma who were 8-18 years old.

The anonymous questionnaire, which was offered to patients seen in the primary care and adolescent clinics at the hospital, included multiple-choice and open-ended questions designed to explore the youths' feelings about their disease and its effect on their lives.

One-third of the respondents had negative feelings about their asthma, and nearly 40% reported that their diagnosis made them feel different from their healthy peers.

“Outward reminders of their asthma made the kids particularly self-conscious,” Ms. Brimer stated. “Many of them—more than one third—said they felt uncomfortable using an inhaler in front of their friends.”

Although nearly 94% of the youth said they enjoyed participating in group activities, especially recreational sports, 45% said they felt restricted or excluded from school activities because of their asthma. “This tells us that maybe we should be looking for ways to incorporate the social preference for team or group activities into an intervention, such as an asthma club,” said Ms. Brimer. “The desire to belong to a group is a powerful motivator, especially among adolescents. There may be ways to use that desire to help asthmatic youth adjust to the disease and its treatment regimen.”

BOSTON — Having asthma can make adolescent patients feel different from their peers, “and there is nothing worse to an adolescent than feeling different,” according to Alysa Brimer, a medical student at the University of Missouri, Kansas City.

In addition to the negative social consequences of asthma—including lack of participation in school-based clubs, athletics, and social events—this negative self-perception may decrease patients' compliance with their medication regimens.

Creating social clubs and group athletic activities exclusively for asthmatic youths may go a long way toward mitigating patients' damaged self-esteem and increasing the likelihood of treatment compliance, Ms. Brimer said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Ms. Brimer and colleagues at Children's Mercy Hospital in Kansas City, Missouri, investigated the factors that make asthmatic youths feel different from their healthy friends, and hypothesized that groups made up of asthmatic peers might improve their self-perception.

The investigators reviewed data from an ongoing survey of children with asthma who were 8-18 years old.

The anonymous questionnaire, which was offered to patients seen in the primary care and adolescent clinics at the hospital, included multiple-choice and open-ended questions designed to explore the youths' feelings about their disease and its effect on their lives.

One-third of the respondents had negative feelings about their asthma, and nearly 40% reported that their diagnosis made them feel different from their healthy peers.

“Outward reminders of their asthma made the kids particularly self-conscious,” Ms. Brimer stated. “Many of them—more than one third—said they felt uncomfortable using an inhaler in front of their friends.”

Although nearly 94% of the youth said they enjoyed participating in group activities, especially recreational sports, 45% said they felt restricted or excluded from school activities because of their asthma. “This tells us that maybe we should be looking for ways to incorporate the social preference for team or group activities into an intervention, such as an asthma club,” said Ms. Brimer. “The desire to belong to a group is a powerful motivator, especially among adolescents. There may be ways to use that desire to help asthmatic youth adjust to the disease and its treatment regimen.”

BOSTON — Having asthma can make adolescent patients feel different from their peers, “and there is nothing worse to an adolescent than feeling different,” according to Alysa Brimer, a medical student at the University of Missouri, Kansas City.

In addition to the negative social consequences of asthma—including lack of participation in school-based clubs, athletics, and social events—this negative self-perception may decrease patients' compliance with their medication regimens.

Creating social clubs and group athletic activities exclusively for asthmatic youths may go a long way toward mitigating patients' damaged self-esteem and increasing the likelihood of treatment compliance, Ms. Brimer said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Ms. Brimer and colleagues at Children's Mercy Hospital in Kansas City, Missouri, investigated the factors that make asthmatic youths feel different from their healthy friends, and hypothesized that groups made up of asthmatic peers might improve their self-perception.

The investigators reviewed data from an ongoing survey of children with asthma who were 8-18 years old.

The anonymous questionnaire, which was offered to patients seen in the primary care and adolescent clinics at the hospital, included multiple-choice and open-ended questions designed to explore the youths' feelings about their disease and its effect on their lives.

One-third of the respondents had negative feelings about their asthma, and nearly 40% reported that their diagnosis made them feel different from their healthy peers.

“Outward reminders of their asthma made the kids particularly self-conscious,” Ms. Brimer stated. “Many of them—more than one third—said they felt uncomfortable using an inhaler in front of their friends.”

Although nearly 94% of the youth said they enjoyed participating in group activities, especially recreational sports, 45% said they felt restricted or excluded from school activities because of their asthma. “This tells us that maybe we should be looking for ways to incorporate the social preference for team or group activities into an intervention, such as an asthma club,” said Ms. Brimer. “The desire to belong to a group is a powerful motivator, especially among adolescents. There may be ways to use that desire to help asthmatic youth adjust to the disease and its treatment regimen.”

BOSTON — Obesity has little impact on the disease-related outcomes of asthma in children, despite the fact that being overweight is an established risk factor for the respiratory condition, reported Umit B. Emre, M.D.

Unlike adults, in whom obesity is associated with higher asthma morbidity, obese or overweight children with asthma have symptoms and morbidity that are “more or less comparable” with those of normal-weight children, Dr. Emre said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Emre and colleagues at Beth Israel Medical Center in New York analyzed data from 85 children and adolescents who were evaluated for asthma at a community-based pediatric pulmonary practice from 1999 to 2003. Asthma was the primary diagnosis for all of the children included in the analysis, and there were no other diseases present. Baseline characteristics, including age, gender, and race, were similar across the group.

The investigators classified the children by asthma severity and by weight using standard body mass index measures. With respect to asthma severity, 32 of the patients were classified as having intermittent asthma, 42 had persistent mild asthma, and 11 had persistent moderate-severe asthma. In terms of weight status, 31 were classified as normal weight, 21 were overweight, and 33 were obese.

The disease severity proportions did not differ between normal, overweight, and obese children, said Dr. Emre. Drug use, emergency treatments, and lung-function test performance were also similar across the board.

Asthma severity, while not predicted by obesity, was itself a predictor of controller therapy use and emergency department visit and/or hospitalization. “As could be expected, rates of drug use and emergency care were highest for children classified as having persistent moderate to severe asthma,” Dr. Emre commented. “Weight classification was not a determinant for either of these outcomes.”

Weight also was not independently correlated with lung function in these patients. The mean forced expiratory volume in 1 second for both the overweight/obese and normal weight groups was approximately 83% of predicted flow, and the mean peak expiratory flow in midlung volume for both was approximately 77% of predicted volume, independent of body mass index.

The study may be limited by selection bias in that the patients were not randomly selected, and all those included had more serious asthma than that which might be seen in the normal pediatric practice, making it more difficult to detect differences that might be related to weight. “Or it may just be that the link becomes more significant over time, as other problems associated with obesity become more problematic, possibly exacerbating asthma symptoms,” he said.

To better understand the full impact of obesity on asthma in young patients, Dr. Emre and colleagues have undertaken a prospective study to address the inherent limitations to a retrospective analysis. “We're looking at different asthma-related disease outcomes, including quality of life, and are trying to detect any weight-based differences,” he noted.

BOSTON — Obesity has little impact on the disease-related outcomes of asthma in children, despite the fact that being overweight is an established risk factor for the respiratory condition, reported Umit B. Emre, M.D.

Unlike adults, in whom obesity is associated with higher asthma morbidity, obese or overweight children with asthma have symptoms and morbidity that are “more or less comparable” with those of normal-weight children, Dr. Emre said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Emre and colleagues at Beth Israel Medical Center in New York analyzed data from 85 children and adolescents who were evaluated for asthma at a community-based pediatric pulmonary practice from 1999 to 2003. Asthma was the primary diagnosis for all of the children included in the analysis, and there were no other diseases present. Baseline characteristics, including age, gender, and race, were similar across the group.

The investigators classified the children by asthma severity and by weight using standard body mass index measures. With respect to asthma severity, 32 of the patients were classified as having intermittent asthma, 42 had persistent mild asthma, and 11 had persistent moderate-severe asthma. In terms of weight status, 31 were classified as normal weight, 21 were overweight, and 33 were obese.

The disease severity proportions did not differ between normal, overweight, and obese children, said Dr. Emre. Drug use, emergency treatments, and lung-function test performance were also similar across the board.

Asthma severity, while not predicted by obesity, was itself a predictor of controller therapy use and emergency department visit and/or hospitalization. “As could be expected, rates of drug use and emergency care were highest for children classified as having persistent moderate to severe asthma,” Dr. Emre commented. “Weight classification was not a determinant for either of these outcomes.”

Weight also was not independently correlated with lung function in these patients. The mean forced expiratory volume in 1 second for both the overweight/obese and normal weight groups was approximately 83% of predicted flow, and the mean peak expiratory flow in midlung volume for both was approximately 77% of predicted volume, independent of body mass index.

The study may be limited by selection bias in that the patients were not randomly selected, and all those included had more serious asthma than that which might be seen in the normal pediatric practice, making it more difficult to detect differences that might be related to weight. “Or it may just be that the link becomes more significant over time, as other problems associated with obesity become more problematic, possibly exacerbating asthma symptoms,” he said.

To better understand the full impact of obesity on asthma in young patients, Dr. Emre and colleagues have undertaken a prospective study to address the inherent limitations to a retrospective analysis. “We're looking at different asthma-related disease outcomes, including quality of life, and are trying to detect any weight-based differences,” he noted.

BOSTON — Obesity has little impact on the disease-related outcomes of asthma in children, despite the fact that being overweight is an established risk factor for the respiratory condition, reported Umit B. Emre, M.D.

Unlike adults, in whom obesity is associated with higher asthma morbidity, obese or overweight children with asthma have symptoms and morbidity that are “more or less comparable” with those of normal-weight children, Dr. Emre said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Emre and colleagues at Beth Israel Medical Center in New York analyzed data from 85 children and adolescents who were evaluated for asthma at a community-based pediatric pulmonary practice from 1999 to 2003. Asthma was the primary diagnosis for all of the children included in the analysis, and there were no other diseases present. Baseline characteristics, including age, gender, and race, were similar across the group.

The investigators classified the children by asthma severity and by weight using standard body mass index measures. With respect to asthma severity, 32 of the patients were classified as having intermittent asthma, 42 had persistent mild asthma, and 11 had persistent moderate-severe asthma. In terms of weight status, 31 were classified as normal weight, 21 were overweight, and 33 were obese.

The disease severity proportions did not differ between normal, overweight, and obese children, said Dr. Emre. Drug use, emergency treatments, and lung-function test performance were also similar across the board.

Asthma severity, while not predicted by obesity, was itself a predictor of controller therapy use and emergency department visit and/or hospitalization. “As could be expected, rates of drug use and emergency care were highest for children classified as having persistent moderate to severe asthma,” Dr. Emre commented. “Weight classification was not a determinant for either of these outcomes.”

Weight also was not independently correlated with lung function in these patients. The mean forced expiratory volume in 1 second for both the overweight/obese and normal weight groups was approximately 83% of predicted flow, and the mean peak expiratory flow in midlung volume for both was approximately 77% of predicted volume, independent of body mass index.

The study may be limited by selection bias in that the patients were not randomly selected, and all those included had more serious asthma than that which might be seen in the normal pediatric practice, making it more difficult to detect differences that might be related to weight. “Or it may just be that the link becomes more significant over time, as other problems associated with obesity become more problematic, possibly exacerbating asthma symptoms,” he said.

To better understand the full impact of obesity on asthma in young patients, Dr. Emre and colleagues have undertaken a prospective study to address the inherent limitations to a retrospective analysis. “We're looking at different asthma-related disease outcomes, including quality of life, and are trying to detect any weight-based differences,” he noted.

BOSTON — High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's “surprising” findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end, Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 HIV-positive breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and AZT. Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. “What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels” of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels were 0.8-47 times the IC50 levels, which “was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be,” said Dr. Shapiro. The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a “two-for-one” deal, he said. “It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly,” he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have acquired HIV in utero or during birth. “It may be that exposure to lower-than-therapeutic drug levels could cause resistance mutations to develop, potentially compromising future treatment,” said Dr. Shapiro. It also is possible that exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

Dr. Shapiro reported that neither he nor his coinvestigators have a financial interest in the manufacturers of the drugs used in the study.

BOSTON — High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's “surprising” findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end, Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 HIV-positive breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and AZT. Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. “What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels” of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels were 0.8-47 times the IC50 levels, which “was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be,” said Dr. Shapiro. The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a “two-for-one” deal, he said. “It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly,” he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have acquired HIV in utero or during birth. “It may be that exposure to lower-than-therapeutic drug levels could cause resistance mutations to develop, potentially compromising future treatment,” said Dr. Shapiro. It also is possible that exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

Dr. Shapiro reported that neither he nor his coinvestigators have a financial interest in the manufacturers of the drugs used in the study.

BOSTON — High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's “surprising” findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end, Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 HIV-positive breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and AZT. Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. “What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels” of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels were 0.8-47 times the IC50 levels, which “was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be,” said Dr. Shapiro. The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a “two-for-one” deal, he said. “It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly,” he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have acquired HIV in utero or during birth. “It may be that exposure to lower-than-therapeutic drug levels could cause resistance mutations to develop, potentially compromising future treatment,” said Dr. Shapiro. It also is possible that exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

Dr. Shapiro reported that neither he nor his coinvestigators have a financial interest in the manufacturers of the drugs used in the study.

BOSTON — Almost half of HIV-positive individuals in the United States who meet federal guidelines for antiretroviral therapy may not be receiving the treatment, according to a recent estimate by the Centers for Disease Control and Prevention.

Late diagnoses, unawareness of HIV risk factors and risk status, and treatment inaccessibility are among the likely factors contributing to the insufficient care of as many as 44% of the country's treatment-eligible HIV-positive individuals, CDC medical epidemiologist Eyasu Teshale, M.D., reported at a conference on retroviruses and opportunistic infections.

Using data from an analysis of AIDS diagnoses reported by all 50 states and HIV diagnoses reported by 30 states with well-established integrated HIV/AIDS reporting systems and lab-based CD4 reports, the CDC investigators estimated that, through 2003, there were about 480,000 treatment-eligible HIV/AIDS patients in this country.

Federal treatment guidelines recommend antiretroviral therapy for HIV-infected patients with CD4 white blood cell counts of 350 cells/μL or lower; yet according to a statistical model, only 56% of eligible patients likely received the recommended therapy, said Dr. Teshale.

To estimate the number of HIV/AIDS patients receiving antiretroviral therapy, the CDC investigators extrapolated treatment percentages from CDC's Adult/Adolescent Spectrum of HIV Disease (ASD) project, a 10-city medical records-based surveillance project that prospectively collected information from more than 60,000 HIV/AIDS patients from 1990 through June 2004.

About 79% of the HIV-infected patients in the ASD population with CD4 counts below 350 cells/μL received antiretroviral therapy. “We applied that proportion to the 340,000 patients estimated to be 'in care' on a national level,” Dr. Teshale said. Using this approach, the investigators estimated that 268,000 (79%) of the 340,000 patients diagnosed and receiving care in the U.S. received ART at the end of 2003. These 268,000 people represent only about 56% of the 480,000 Americans aged 15-49 who were living with HIV/AIDS and were eligible for ART at the end of 2003.

An estimated 42% of eligible patients not getting antiretroviral therapy have not even been diagnosed with HIV infection, and as many as 25% are likely aware of their HIV status but are not receiving medical care for it, Dr. Teshale said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Among patients who have access to health care and are being treated for HIV, barriers to receiving recommended antiretroviral treatment include the expense of the multidrug cocktails, which can cost more than $10,000 per year. Although private insurance will often cover this expense, patients receiving public health assistance are often placed on waiting lists for the drugs. Finally, some patients choose not to take the antiretroviral medications because of the side effects.

The new estimates, though limited by variations in data collection by states and inconsistencies in the medical records included in the analyses, support previous research demonstrating the unmet need for antiretroviral therapy.

The findings need to be validated by additional research, and the factors contributing to insufficient care for HIV-infected individuals deserve more study.

However, efforts to reduce the scope of the problem should be implemented without waiting for further research, Dr. Teshale said. These include increasing individuals' awareness of their HIV status, providing more methods for linking at-risk individuals to prevention and care programs, and encouraging health care providers to prescribe antiretroviral therapy, according to federal guidelines.

BOSTON — Almost half of HIV-positive individuals in the United States who meet federal guidelines for antiretroviral therapy may not be receiving the treatment, according to a recent estimate by the Centers for Disease Control and Prevention.

Late diagnoses, unawareness of HIV risk factors and risk status, and treatment inaccessibility are among the likely factors contributing to the insufficient care of as many as 44% of the country's treatment-eligible HIV-positive individuals, CDC medical epidemiologist Eyasu Teshale, M.D., reported at a conference on retroviruses and opportunistic infections.

Using data from an analysis of AIDS diagnoses reported by all 50 states and HIV diagnoses reported by 30 states with well-established integrated HIV/AIDS reporting systems and lab-based CD4 reports, the CDC investigators estimated that, through 2003, there were about 480,000 treatment-eligible HIV/AIDS patients in this country.

Federal treatment guidelines recommend antiretroviral therapy for HIV-infected patients with CD4 white blood cell counts of 350 cells/μL or lower; yet according to a statistical model, only 56% of eligible patients likely received the recommended therapy, said Dr. Teshale.

To estimate the number of HIV/AIDS patients receiving antiretroviral therapy, the CDC investigators extrapolated treatment percentages from CDC's Adult/Adolescent Spectrum of HIV Disease (ASD) project, a 10-city medical records-based surveillance project that prospectively collected information from more than 60,000 HIV/AIDS patients from 1990 through June 2004.

About 79% of the HIV-infected patients in the ASD population with CD4 counts below 350 cells/μL received antiretroviral therapy. “We applied that proportion to the 340,000 patients estimated to be 'in care' on a national level,” Dr. Teshale said. Using this approach, the investigators estimated that 268,000 (79%) of the 340,000 patients diagnosed and receiving care in the U.S. received ART at the end of 2003. These 268,000 people represent only about 56% of the 480,000 Americans aged 15-49 who were living with HIV/AIDS and were eligible for ART at the end of 2003.

An estimated 42% of eligible patients not getting antiretroviral therapy have not even been diagnosed with HIV infection, and as many as 25% are likely aware of their HIV status but are not receiving medical care for it, Dr. Teshale said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Among patients who have access to health care and are being treated for HIV, barriers to receiving recommended antiretroviral treatment include the expense of the multidrug cocktails, which can cost more than $10,000 per year. Although private insurance will often cover this expense, patients receiving public health assistance are often placed on waiting lists for the drugs. Finally, some patients choose not to take the antiretroviral medications because of the side effects.

The new estimates, though limited by variations in data collection by states and inconsistencies in the medical records included in the analyses, support previous research demonstrating the unmet need for antiretroviral therapy.

The findings need to be validated by additional research, and the factors contributing to insufficient care for HIV-infected individuals deserve more study.

However, efforts to reduce the scope of the problem should be implemented without waiting for further research, Dr. Teshale said. These include increasing individuals' awareness of their HIV status, providing more methods for linking at-risk individuals to prevention and care programs, and encouraging health care providers to prescribe antiretroviral therapy, according to federal guidelines.

BOSTON — Almost half of HIV-positive individuals in the United States who meet federal guidelines for antiretroviral therapy may not be receiving the treatment, according to a recent estimate by the Centers for Disease Control and Prevention.

Late diagnoses, unawareness of HIV risk factors and risk status, and treatment inaccessibility are among the likely factors contributing to the insufficient care of as many as 44% of the country's treatment-eligible HIV-positive individuals, CDC medical epidemiologist Eyasu Teshale, M.D., reported at a conference on retroviruses and opportunistic infections.

Using data from an analysis of AIDS diagnoses reported by all 50 states and HIV diagnoses reported by 30 states with well-established integrated HIV/AIDS reporting systems and lab-based CD4 reports, the CDC investigators estimated that, through 2003, there were about 480,000 treatment-eligible HIV/AIDS patients in this country.

Federal treatment guidelines recommend antiretroviral therapy for HIV-infected patients with CD4 white blood cell counts of 350 cells/μL or lower; yet according to a statistical model, only 56% of eligible patients likely received the recommended therapy, said Dr. Teshale.

To estimate the number of HIV/AIDS patients receiving antiretroviral therapy, the CDC investigators extrapolated treatment percentages from CDC's Adult/Adolescent Spectrum of HIV Disease (ASD) project, a 10-city medical records-based surveillance project that prospectively collected information from more than 60,000 HIV/AIDS patients from 1990 through June 2004.

About 79% of the HIV-infected patients in the ASD population with CD4 counts below 350 cells/μL received antiretroviral therapy. “We applied that proportion to the 340,000 patients estimated to be 'in care' on a national level,” Dr. Teshale said. Using this approach, the investigators estimated that 268,000 (79%) of the 340,000 patients diagnosed and receiving care in the U.S. received ART at the end of 2003. These 268,000 people represent only about 56% of the 480,000 Americans aged 15-49 who were living with HIV/AIDS and were eligible for ART at the end of 2003.

An estimated 42% of eligible patients not getting antiretroviral therapy have not even been diagnosed with HIV infection, and as many as 25% are likely aware of their HIV status but are not receiving medical care for it, Dr. Teshale said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Among patients who have access to health care and are being treated for HIV, barriers to receiving recommended antiretroviral treatment include the expense of the multidrug cocktails, which can cost more than $10,000 per year. Although private insurance will often cover this expense, patients receiving public health assistance are often placed on waiting lists for the drugs. Finally, some patients choose not to take the antiretroviral medications because of the side effects.

The new estimates, though limited by variations in data collection by states and inconsistencies in the medical records included in the analyses, support previous research demonstrating the unmet need for antiretroviral therapy.

The findings need to be validated by additional research, and the factors contributing to insufficient care for HIV-infected individuals deserve more study.

However, efforts to reduce the scope of the problem should be implemented without waiting for further research, Dr. Teshale said. These include increasing individuals' awareness of their HIV status, providing more methods for linking at-risk individuals to prevention and care programs, and encouraging health care providers to prescribe antiretroviral therapy, according to federal guidelines.

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.

“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the NCCN.

Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.

Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.

In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.

The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.

And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not.

Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis.

“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.

It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.

HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.

“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the NCCN.

Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.

Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.

In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.

The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.

And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not.

Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis.

“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.

It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.

HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.

“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the NCCN.

Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.

Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.

In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.

The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.

And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not.

Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis.

“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.

It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.

HOLLYWOOD, FLA. — New guidelines have broadened the options for adjuvant chemotherapy in colon cancer patients who are at high risk of recurrence to include the alkylating agent oxaliplatin and the antimetabolite drug capecitabine.

In the adjuvant setting, patients with stage III colon cancer (tumor-node-metastasis T1-3, N1-2 [any lymph node involvement], M0) should receive oxaliplatin with 5-fluorouracil (5-FU) and leucovorin (the FOLFOX regimen); or capecitabine (Xeloda); or 5-FU and leucovorin without oxaliplatin, Paul Engstrom, M.D., said when presenting the updated guidelines at the annual conference of the National Comprehensive Cancer Network (NCCN).

The updates reflect large-scale clinical trial findings, said Dr. Engstrom, chair of the NCCN colon cancer guideline panel.

The oxaliplatin recommendation is based on findings from the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) study in which investigators compared the toxic effects and efficacy of the three-drug FOLFOX regimen against that of the 5-FU/-leucovorin regimen. The study, which included about 2,200 patients with resected stage II or stage III colon cancer randomized to 6 months of treatment with one of the two regimens, showed stage III patients receiving FOLFOX had a 24% reduction in their relative risk of disease recurrence after 3 years, compared with the non-oxaliplatin group.

The data showed a significant disease-free survival benefit for stage III patients, but not for stage II patients, said Dr. Engstrom of the Fox Chase Cancer Center, Philadelphia.

Given the incidence of oxaliplatin-associated toxicities—41% of patients experienced neutropenia higher than grade III, and 12.4% experienced reversible grade III peripheral sensorial neuropathy—the new guidelines do not recommend the FOLFOX regimen for most stage II patients, Dr. Engstrom said.

The oxaliplatin-containing regimen may be an option for patients with stage II colon cancer who are considered to be at high risk for cancer recurrence based on primary tumor staging, the guidelines state.

The capecitabine recommendation reflects the findings of the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial of nearly 2,000 patients with stage III disease randomized to receive capecitabine or intravenous 5-FU/leucovorin following tumor resection. Taken orally, capecitabine is converted by the body into 5-FU. The X-ACT results showed capecitabine had better disease-free survival and overall survival rates than the 5-FU/leucovorin regimen and caused significantly fewer serious side effects, although hand-and-foot syndrome was significantly more common in the capecitabine group, he said.

The added options for adjuvant colon cancer therapy have contributed to a sense of optimism in treatment. Because the guidelines give equal weight to the adjuvant therapy recommendations, the choice of which regimen to use should depend on the risk to the patient, he said.

Last updated in 2004, the colon cancer guidelines also include these changes:

▸ Distinctions between three levels of stage III disease (stages IIIA, IIIB, and IIIC) to better target therapeutic decisions.

▸ The recommendation that radiotherapy be considered for use in combination with 5-FU/leucovorin for patients with advanced stage III disease with tumors that have invaded other organs or structures or have perforated the visceral peritoneum, and those with one or two regional metastases.

▸ The inclusion of a restructured treatment algorithm that includes chemotherapy with bevacizumab (Avastin) for patients with advanced colon cancer, giving equal weight to all of the commonly used regimens, including FOLFOX, FOLFIRI (5-FU/leucovorin/irinotecan), irinotecan and bolus 5-FU/leucovorin—all with or without bevacizumab—and 5-FU/leucovorin with bevacizumab.

▸ A recommendation that computed tomography be explored in the surveillance period for those at high risk of recurrence.

▸ A suggestion that laparoscopic surgery be considered instead of open surgery for resection of limited disease.

▸ A recommendation that staging of disease following primary resection of the tumor should be based on results from sampling a minimum of 12 lymph nodes.

▸ The addition of a section regarding risk assessment for stage II disease that recommends physician/patient discussion about treatment options and factors to consider when determining whether adjuvant therapy should be administered.

The NCCN is an alliance of 19 institutions designated comprehensive cancer centers by the National Cancer Institute.

HOLLYWOOD, FLA. — New guidelines have broadened the options for adjuvant chemotherapy in colon cancer patients who are at high risk of recurrence to include the alkylating agent oxaliplatin and the antimetabolite drug capecitabine.

In the adjuvant setting, patients with stage III colon cancer (tumor-node-metastasis T1-3, N1-2 [any lymph node involvement], M0) should receive oxaliplatin with 5-fluorouracil (5-FU) and leucovorin (the FOLFOX regimen); or capecitabine (Xeloda); or 5-FU and leucovorin without oxaliplatin, Paul Engstrom, M.D., said when presenting the updated guidelines at the annual conference of the National Comprehensive Cancer Network (NCCN).

The updates reflect large-scale clinical trial findings, said Dr. Engstrom, chair of the NCCN colon cancer guideline panel.

The oxaliplatin recommendation is based on findings from the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) study in which investigators compared the toxic effects and efficacy of the three-drug FOLFOX regimen against that of the 5-FU/-leucovorin regimen. The study, which included about 2,200 patients with resected stage II or stage III colon cancer randomized to 6 months of treatment with one of the two regimens, showed stage III patients receiving FOLFOX had a 24% reduction in their relative risk of disease recurrence after 3 years, compared with the non-oxaliplatin group.

The data showed a significant disease-free survival benefit for stage III patients, but not for stage II patients, said Dr. Engstrom of the Fox Chase Cancer Center, Philadelphia.

Given the incidence of oxaliplatin-associated toxicities—41% of patients experienced neutropenia higher than grade III, and 12.4% experienced reversible grade III peripheral sensorial neuropathy—the new guidelines do not recommend the FOLFOX regimen for most stage II patients, Dr. Engstrom said.

The oxaliplatin-containing regimen may be an option for patients with stage II colon cancer who are considered to be at high risk for cancer recurrence based on primary tumor staging, the guidelines state.

The capecitabine recommendation reflects the findings of the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial of nearly 2,000 patients with stage III disease randomized to receive capecitabine or intravenous 5-FU/leucovorin following tumor resection. Taken orally, capecitabine is converted by the body into 5-FU. The X-ACT results showed capecitabine had better disease-free survival and overall survival rates than the 5-FU/leucovorin regimen and caused significantly fewer serious side effects, although hand-and-foot syndrome was significantly more common in the capecitabine group, he said.

The added options for adjuvant colon cancer therapy have contributed to a sense of optimism in treatment. Because the guidelines give equal weight to the adjuvant therapy recommendations, the choice of which regimen to use should depend on the risk to the patient, he said.

Last updated in 2004, the colon cancer guidelines also include these changes:

▸ Distinctions between three levels of stage III disease (stages IIIA, IIIB, and IIIC) to better target therapeutic decisions.

▸ The recommendation that radiotherapy be considered for use in combination with 5-FU/leucovorin for patients with advanced stage III disease with tumors that have invaded other organs or structures or have perforated the visceral peritoneum, and those with one or two regional metastases.

▸ The inclusion of a restructured treatment algorithm that includes chemotherapy with bevacizumab (Avastin) for patients with advanced colon cancer, giving equal weight to all of the commonly used regimens, including FOLFOX, FOLFIRI (5-FU/leucovorin/irinotecan), irinotecan and bolus 5-FU/leucovorin—all with or without bevacizumab—and 5-FU/leucovorin with bevacizumab.

▸ A recommendation that computed tomography be explored in the surveillance period for those at high risk of recurrence.

▸ A suggestion that laparoscopic surgery be considered instead of open surgery for resection of limited disease.

▸ A recommendation that staging of disease following primary resection of the tumor should be based on results from sampling a minimum of 12 lymph nodes.

▸ The addition of a section regarding risk assessment for stage II disease that recommends physician/patient discussion about treatment options and factors to consider when determining whether adjuvant therapy should be administered.

The NCCN is an alliance of 19 institutions designated comprehensive cancer centers by the National Cancer Institute.

HOLLYWOOD, FLA. — New guidelines have broadened the options for adjuvant chemotherapy in colon cancer patients who are at high risk of recurrence to include the alkylating agent oxaliplatin and the antimetabolite drug capecitabine.

In the adjuvant setting, patients with stage III colon cancer (tumor-node-metastasis T1-3, N1-2 [any lymph node involvement], M0) should receive oxaliplatin with 5-fluorouracil (5-FU) and leucovorin (the FOLFOX regimen); or capecitabine (Xeloda); or 5-FU and leucovorin without oxaliplatin, Paul Engstrom, M.D., said when presenting the updated guidelines at the annual conference of the National Comprehensive Cancer Network (NCCN).

The updates reflect large-scale clinical trial findings, said Dr. Engstrom, chair of the NCCN colon cancer guideline panel.

The oxaliplatin recommendation is based on findings from the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) study in which investigators compared the toxic effects and efficacy of the three-drug FOLFOX regimen against that of the 5-FU/-leucovorin regimen. The study, which included about 2,200 patients with resected stage II or stage III colon cancer randomized to 6 months of treatment with one of the two regimens, showed stage III patients receiving FOLFOX had a 24% reduction in their relative risk of disease recurrence after 3 years, compared with the non-oxaliplatin group.

The data showed a significant disease-free survival benefit for stage III patients, but not for stage II patients, said Dr. Engstrom of the Fox Chase Cancer Center, Philadelphia.

Given the incidence of oxaliplatin-associated toxicities—41% of patients experienced neutropenia higher than grade III, and 12.4% experienced reversible grade III peripheral sensorial neuropathy—the new guidelines do not recommend the FOLFOX regimen for most stage II patients, Dr. Engstrom said.

The oxaliplatin-containing regimen may be an option for patients with stage II colon cancer who are considered to be at high risk for cancer recurrence based on primary tumor staging, the guidelines state.

The capecitabine recommendation reflects the findings of the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial of nearly 2,000 patients with stage III disease randomized to receive capecitabine or intravenous 5-FU/leucovorin following tumor resection. Taken orally, capecitabine is converted by the body into 5-FU. The X-ACT results showed capecitabine had better disease-free survival and overall survival rates than the 5-FU/leucovorin regimen and caused significantly fewer serious side effects, although hand-and-foot syndrome was significantly more common in the capecitabine group, he said.

The added options for adjuvant colon cancer therapy have contributed to a sense of optimism in treatment. Because the guidelines give equal weight to the adjuvant therapy recommendations, the choice of which regimen to use should depend on the risk to the patient, he said.

Last updated in 2004, the colon cancer guidelines also include these changes:

▸ Distinctions between three levels of stage III disease (stages IIIA, IIIB, and IIIC) to better target therapeutic decisions.

▸ The recommendation that radiotherapy be considered for use in combination with 5-FU/leucovorin for patients with advanced stage III disease with tumors that have invaded other organs or structures or have perforated the visceral peritoneum, and those with one or two regional metastases.

▸ The inclusion of a restructured treatment algorithm that includes chemotherapy with bevacizumab (Avastin) for patients with advanced colon cancer, giving equal weight to all of the commonly used regimens, including FOLFOX, FOLFIRI (5-FU/leucovorin/irinotecan), irinotecan and bolus 5-FU/leucovorin—all with or without bevacizumab—and 5-FU/leucovorin with bevacizumab.

▸ A recommendation that computed tomography be explored in the surveillance period for those at high risk of recurrence.

▸ A suggestion that laparoscopic surgery be considered instead of open surgery for resection of limited disease.

▸ A recommendation that staging of disease following primary resection of the tumor should be based on results from sampling a minimum of 12 lymph nodes.

▸ The addition of a section regarding risk assessment for stage II disease that recommends physician/patient discussion about treatment options and factors to consider when determining whether adjuvant therapy should be administered.

The NCCN is an alliance of 19 institutions designated comprehensive cancer centers by the National Cancer Institute.