Jennie Smith

The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.

The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.

Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.

The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.

The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.

"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.

For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.

All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.

The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.

The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.

Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."

"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.

The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.

The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.

The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.

Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.

The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.

The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.

"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.

For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.

All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.

The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.

The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.

Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."

"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.

The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.

The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.

The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.

Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.

The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.

The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.

"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.

For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.

All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.

The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.

The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.

Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."

"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.

The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.

The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.

The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.

Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.

The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.

The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.

"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.

For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.

All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.

The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.

The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.

Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."

"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.

The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.

The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.

The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.

Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.

The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.

The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.

"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.

For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.

All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.

The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.

The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.

Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."

"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.

The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.

The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.

The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.

Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.

The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.

The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.

"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.

For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.

All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.

The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.

The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.

Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."

"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.

The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.

A two-tiered system of surveillance could reduce prostate cancer deaths by half while also curbing overdiagnosis and overtreatment, according to results from a large Swedish study.

The system would allow men who test for high levels of prostate-specific antigen (more than 1.6 ng/mL) in their 40s to undergo close surveillance as they age, while the rest – approximately half of all men – would need to be tested only three times between the ages of 44 and 60 years.

The findings, released May 18 and highlighted during a press briefing at which the American Society of Clinical Oncology offered a preview of studies to be presented at its annual meeting in June, could help lead to a more "rational" screening strategy, according to the study’s investigators.

While there is evidence that PSA screening can detect prostate cancer at an early, curable stage, it is viewed as problematic because of the risk of overtreatment. PSA levels are not necessarily indicative of present cancer, and a large number of men must be screened to prevent a single death.

The investigators, led by Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center in New York, conducted a case-control study nested within a cohort of 12,090 Swedish men who provided blood between 1974 and 1986. A total of 4,999 provided repeat samples 6 years later. The investigators also looked at an independent cohort of 1,167 men who provided blood at age 60 years. Men with evidence of prostate cancer metastasis or death (n = 252) were matched 3:1 with controls.

The study found that 44% of prostate cancer deaths occurred in men who had the top 10% of PSA levels (greater than 1.6 ng/mL) for their age group when they were tested for the first time between the ages of 44 and 50 years.

Men whose PSA levels remained below the median for the population in their age group saw a progressively declining rate of death or metastasis.

The investigators found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44-50 years whose initial screens showed a PSA below the median in the population (0.7 ng/mL).

For men aged 51-55 years with a PSA lower than the median (0.8 ng/mL), the risk of metastatic prostate cancer or death was 18% over 27 years. At age 60 years, only 0.5% of deaths or metastases occurred in men with a PSA less than the median for that age (1.1 ng/mL).

The findings show that PSA levels at the time of initial screening among men aged 44-50 years can accurately predict the risk of death from prostate cancer or metastatic prostate cancer up to 30 years later. Concentrating surveillance in this group of men could allow the rest to undergo only three lifetime tests at the ages of 44, 51-55, and 60 years, the investigators concluded.

Dr. Lilja disclosed owning stock in Arctic Partners, a firm that holds patents for PSA assays.

A two-tiered system of surveillance could reduce prostate cancer deaths by half while also curbing overdiagnosis and overtreatment, according to results from a large Swedish study.

The system would allow men who test for high levels of prostate-specific antigen (more than 1.6 ng/mL) in their 40s to undergo close surveillance as they age, while the rest – approximately half of all men – would need to be tested only three times between the ages of 44 and 60 years.

The findings, released May 18 and highlighted during a press briefing at which the American Society of Clinical Oncology offered a preview of studies to be presented at its annual meeting in June, could help lead to a more "rational" screening strategy, according to the study’s investigators.

While there is evidence that PSA screening can detect prostate cancer at an early, curable stage, it is viewed as problematic because of the risk of overtreatment. PSA levels are not necessarily indicative of present cancer, and a large number of men must be screened to prevent a single death.

The investigators, led by Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center in New York, conducted a case-control study nested within a cohort of 12,090 Swedish men who provided blood between 1974 and 1986. A total of 4,999 provided repeat samples 6 years later. The investigators also looked at an independent cohort of 1,167 men who provided blood at age 60 years. Men with evidence of prostate cancer metastasis or death (n = 252) were matched 3:1 with controls.

The study found that 44% of prostate cancer deaths occurred in men who had the top 10% of PSA levels (greater than 1.6 ng/mL) for their age group when they were tested for the first time between the ages of 44 and 50 years.

Men whose PSA levels remained below the median for the population in their age group saw a progressively declining rate of death or metastasis.

The investigators found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44-50 years whose initial screens showed a PSA below the median in the population (0.7 ng/mL).

For men aged 51-55 years with a PSA lower than the median (0.8 ng/mL), the risk of metastatic prostate cancer or death was 18% over 27 years. At age 60 years, only 0.5% of deaths or metastases occurred in men with a PSA less than the median for that age (1.1 ng/mL).

The findings show that PSA levels at the time of initial screening among men aged 44-50 years can accurately predict the risk of death from prostate cancer or metastatic prostate cancer up to 30 years later. Concentrating surveillance in this group of men could allow the rest to undergo only three lifetime tests at the ages of 44, 51-55, and 60 years, the investigators concluded.

Dr. Lilja disclosed owning stock in Arctic Partners, a firm that holds patents for PSA assays.

A two-tiered system of surveillance could reduce prostate cancer deaths by half while also curbing overdiagnosis and overtreatment, according to results from a large Swedish study.

The system would allow men who test for high levels of prostate-specific antigen (more than 1.6 ng/mL) in their 40s to undergo close surveillance as they age, while the rest – approximately half of all men – would need to be tested only three times between the ages of 44 and 60 years.

The findings, released May 18 and highlighted during a press briefing at which the American Society of Clinical Oncology offered a preview of studies to be presented at its annual meeting in June, could help lead to a more "rational" screening strategy, according to the study’s investigators.

While there is evidence that PSA screening can detect prostate cancer at an early, curable stage, it is viewed as problematic because of the risk of overtreatment. PSA levels are not necessarily indicative of present cancer, and a large number of men must be screened to prevent a single death.

The investigators, led by Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center in New York, conducted a case-control study nested within a cohort of 12,090 Swedish men who provided blood between 1974 and 1986. A total of 4,999 provided repeat samples 6 years later. The investigators also looked at an independent cohort of 1,167 men who provided blood at age 60 years. Men with evidence of prostate cancer metastasis or death (n = 252) were matched 3:1 with controls.

The study found that 44% of prostate cancer deaths occurred in men who had the top 10% of PSA levels (greater than 1.6 ng/mL) for their age group when they were tested for the first time between the ages of 44 and 50 years.

Men whose PSA levels remained below the median for the population in their age group saw a progressively declining rate of death or metastasis.

The investigators found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44-50 years whose initial screens showed a PSA below the median in the population (0.7 ng/mL).

For men aged 51-55 years with a PSA lower than the median (0.8 ng/mL), the risk of metastatic prostate cancer or death was 18% over 27 years. At age 60 years, only 0.5% of deaths or metastases occurred in men with a PSA less than the median for that age (1.1 ng/mL).

The findings show that PSA levels at the time of initial screening among men aged 44-50 years can accurately predict the risk of death from prostate cancer or metastatic prostate cancer up to 30 years later. Concentrating surveillance in this group of men could allow the rest to undergo only three lifetime tests at the ages of 44, 51-55, and 60 years, the investigators concluded.

Dr. Lilja disclosed owning stock in Arctic Partners, a firm that holds patents for PSA assays.

A two-tiered system of surveillance could reduce prostate cancer deaths by half while also curbing overdiagnosis and overtreatment, according to results from a large Swedish study.

The system would allow men who test for high levels of prostate-specific antigen (more than 1.6 ng/mL) in their 40s to undergo close surveillance as they age, while the rest – approximately half of all men – would need to be tested only three times between the ages of 44 and 60 years.

The findings, released May 18 and highlighted during a press briefing at which the American Society of Clinical Oncology offered a preview of studies to be presented at its annual meeting in June, could help lead to a more "rational" screening strategy, according to the study’s investigators.

While there is evidence that PSA screening can detect prostate cancer at an early, curable stage, it is viewed as problematic because of the risk of overtreatment. PSA levels are not necessarily indicative of present cancer, and a large number of men must be screened to prevent a single death.

The investigators, led by Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center in New York, conducted a case-control study nested within a cohort of 12,090 Swedish men who provided blood between 1974 and 1986. A total of 4,999 provided repeat samples 6 years later. The investigators also looked at an independent cohort of 1,167 men who provided blood at age 60 years. Men with evidence of prostate cancer metastasis or death (n = 252) were matched 3:1 with controls.

The study found that 44% of prostate cancer deaths occurred in men who had the top 10% of PSA levels (greater than 1.6 ng/mL) for their age group when they were tested for the first time between the ages of 44 and 50 years.

Men whose PSA levels remained below the median for the population in their age group saw a progressively declining rate of death or metastasis.

The investigators found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44-50 years whose initial screens showed a PSA below the median in the population (0.7 ng/mL).

For men aged 51-55 years with a PSA lower than the median (0.8 ng/mL), the risk of metastatic prostate cancer or death was 18% over 27 years. At age 60 years, only 0.5% of deaths or metastases occurred in men with a PSA less than the median for that age (1.1 ng/mL).

The findings show that PSA levels at the time of initial screening among men aged 44-50 years can accurately predict the risk of death from prostate cancer or metastatic prostate cancer up to 30 years later. Concentrating surveillance in this group of men could allow the rest to undergo only three lifetime tests at the ages of 44, 51-55, and 60 years, the investigators concluded.

Dr. Lilja disclosed owning stock in Arctic Partners, a firm that holds patents for PSA assays.

A two-tiered system of surveillance could reduce prostate cancer deaths by half while also curbing overdiagnosis and overtreatment, according to results from a large Swedish study.

The system would allow men who test for high levels of prostate-specific antigen (more than 1.6 ng/mL) in their 40s to undergo close surveillance as they age, while the rest – approximately half of all men – would need to be tested only three times between the ages of 44 and 60 years.

The findings, released May 18 and highlighted during a press briefing at which the American Society of Clinical Oncology offered a preview of studies to be presented at its annual meeting in June, could help lead to a more "rational" screening strategy, according to the study’s investigators.

While there is evidence that PSA screening can detect prostate cancer at an early, curable stage, it is viewed as problematic because of the risk of overtreatment. PSA levels are not necessarily indicative of present cancer, and a large number of men must be screened to prevent a single death.

The investigators, led by Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center in New York, conducted a case-control study nested within a cohort of 12,090 Swedish men who provided blood between 1974 and 1986. A total of 4,999 provided repeat samples 6 years later. The investigators also looked at an independent cohort of 1,167 men who provided blood at age 60 years. Men with evidence of prostate cancer metastasis or death (n = 252) were matched 3:1 with controls.

The study found that 44% of prostate cancer deaths occurred in men who had the top 10% of PSA levels (greater than 1.6 ng/mL) for their age group when they were tested for the first time between the ages of 44 and 50 years.

Men whose PSA levels remained below the median for the population in their age group saw a progressively declining rate of death or metastasis.

The investigators found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44-50 years whose initial screens showed a PSA below the median in the population (0.7 ng/mL).

For men aged 51-55 years with a PSA lower than the median (0.8 ng/mL), the risk of metastatic prostate cancer or death was 18% over 27 years. At age 60 years, only 0.5% of deaths or metastases occurred in men with a PSA less than the median for that age (1.1 ng/mL).

The findings show that PSA levels at the time of initial screening among men aged 44-50 years can accurately predict the risk of death from prostate cancer or metastatic prostate cancer up to 30 years later. Concentrating surveillance in this group of men could allow the rest to undergo only three lifetime tests at the ages of 44, 51-55, and 60 years, the investigators concluded.

Dr. Lilja disclosed owning stock in Arctic Partners, a firm that holds patents for PSA assays.

A two-tiered system of surveillance could reduce prostate cancer deaths by half while also curbing overdiagnosis and overtreatment, according to results from a large Swedish study.

The system would allow men who test for high levels of prostate-specific antigen (more than 1.6 ng/mL) in their 40s to undergo close surveillance as they age, while the rest – approximately half of all men – would need to be tested only three times between the ages of 44 and 60 years.

The findings, released May 18 and highlighted during a press briefing at which the American Society of Clinical Oncology offered a preview of studies to be presented at its annual meeting in June, could help lead to a more "rational" screening strategy, according to the study’s investigators.

While there is evidence that PSA screening can detect prostate cancer at an early, curable stage, it is viewed as problematic because of the risk of overtreatment. PSA levels are not necessarily indicative of present cancer, and a large number of men must be screened to prevent a single death.

The investigators, led by Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center in New York, conducted a case-control study nested within a cohort of 12,090 Swedish men who provided blood between 1974 and 1986. A total of 4,999 provided repeat samples 6 years later. The investigators also looked at an independent cohort of 1,167 men who provided blood at age 60 years. Men with evidence of prostate cancer metastasis or death (n = 252) were matched 3:1 with controls.

The study found that 44% of prostate cancer deaths occurred in men who had the top 10% of PSA levels (greater than 1.6 ng/mL) for their age group when they were tested for the first time between the ages of 44 and 50 years.

Men whose PSA levels remained below the median for the population in their age group saw a progressively declining rate of death or metastasis.

The investigators found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44-50 years whose initial screens showed a PSA below the median in the population (0.7 ng/mL).

For men aged 51-55 years with a PSA lower than the median (0.8 ng/mL), the risk of metastatic prostate cancer or death was 18% over 27 years. At age 60 years, only 0.5% of deaths or metastases occurred in men with a PSA less than the median for that age (1.1 ng/mL).

The findings show that PSA levels at the time of initial screening among men aged 44-50 years can accurately predict the risk of death from prostate cancer or metastatic prostate cancer up to 30 years later. Concentrating surveillance in this group of men could allow the rest to undergo only three lifetime tests at the ages of 44, 51-55, and 60 years, the investigators concluded.

Dr. Lilja disclosed owning stock in Arctic Partners, a firm that holds patents for PSA assays.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15-35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh, also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the American Society of Clinical Oncology’s annual meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15-35 years.

"An increase in breast cancer risk associated with cigarette smoking had not been established until recently," Dr. Land said at a May 18 press conference announcing the findings and noted that her group’s study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that "healthy lifestyle choices provide women a way to reduce their risk of these four major cancers," Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the investigators’ study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

The investigators also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk.

The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO’s president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land’s study highlighted "the incredible importance of lifestyle factors," and offered a reminder of the need to "think less about drugs and a great deal about whether we can prevent cancer."

The findings, he said, offer "yet another reason to encourage women to stop smoking." Dr. Sledge said he also found the reduced risk of colorectal cancer associated with moderate drinking "very interesting," but that more research would be needed.

The study by Dr. Land and her colleagues was funded by the National Cancer Institute. One of Dr. Land’s coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15-35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh, also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the American Society of Clinical Oncology’s annual meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15-35 years.

"An increase in breast cancer risk associated with cigarette smoking had not been established until recently," Dr. Land said at a May 18 press conference announcing the findings and noted that her group’s study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that "healthy lifestyle choices provide women a way to reduce their risk of these four major cancers," Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the investigators’ study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

The investigators also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk.

The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO’s president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land’s study highlighted "the incredible importance of lifestyle factors," and offered a reminder of the need to "think less about drugs and a great deal about whether we can prevent cancer."

The findings, he said, offer "yet another reason to encourage women to stop smoking." Dr. Sledge said he also found the reduced risk of colorectal cancer associated with moderate drinking "very interesting," but that more research would be needed.

The study by Dr. Land and her colleagues was funded by the National Cancer Institute. One of Dr. Land’s coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15-35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh, also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the American Society of Clinical Oncology’s annual meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15-35 years.

"An increase in breast cancer risk associated with cigarette smoking had not been established until recently," Dr. Land said at a May 18 press conference announcing the findings and noted that her group’s study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that "healthy lifestyle choices provide women a way to reduce their risk of these four major cancers," Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the investigators’ study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

The investigators also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk.

The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO’s president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land’s study highlighted "the incredible importance of lifestyle factors," and offered a reminder of the need to "think less about drugs and a great deal about whether we can prevent cancer."

The findings, he said, offer "yet another reason to encourage women to stop smoking." Dr. Sledge said he also found the reduced risk of colorectal cancer associated with moderate drinking "very interesting," but that more research would be needed.

The study by Dr. Land and her colleagues was funded by the National Cancer Institute. One of Dr. Land’s coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15-35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh, also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the American Society of Clinical Oncology’s annual meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15-35 years.

"An increase in breast cancer risk associated with cigarette smoking had not been established until recently," Dr. Land said at a May 18 press conference announcing the findings and noted that her group’s study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that "healthy lifestyle choices provide women a way to reduce their risk of these four major cancers," Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the investigators’ study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

The investigators also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk.

The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO’s president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land’s study highlighted "the incredible importance of lifestyle factors," and offered a reminder of the need to "think less about drugs and a great deal about whether we can prevent cancer."

The findings, he said, offer "yet another reason to encourage women to stop smoking." Dr. Sledge said he also found the reduced risk of colorectal cancer associated with moderate drinking "very interesting," but that more research would be needed.

The study by Dr. Land and her colleagues was funded by the National Cancer Institute. One of Dr. Land’s coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15-35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh, also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the American Society of Clinical Oncology’s annual meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15-35 years.

"An increase in breast cancer risk associated with cigarette smoking had not been established until recently," Dr. Land said at a May 18 press conference announcing the findings and noted that her group’s study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that "healthy lifestyle choices provide women a way to reduce their risk of these four major cancers," Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the investigators’ study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

The investigators also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk.

The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO’s president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land’s study highlighted "the incredible importance of lifestyle factors," and offered a reminder of the need to "think less about drugs and a great deal about whether we can prevent cancer."

The findings, he said, offer "yet another reason to encourage women to stop smoking." Dr. Sledge said he also found the reduced risk of colorectal cancer associated with moderate drinking "very interesting," but that more research would be needed.

The study by Dr. Land and her colleagues was funded by the National Cancer Institute. One of Dr. Land’s coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15-35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh, also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the American Society of Clinical Oncology’s annual meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15-35 years.

"An increase in breast cancer risk associated with cigarette smoking had not been established until recently," Dr. Land said at a May 18 press conference announcing the findings and noted that her group’s study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that "healthy lifestyle choices provide women a way to reduce their risk of these four major cancers," Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the investigators’ study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

The investigators also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk.

The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO’s president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land’s study highlighted "the incredible importance of lifestyle factors," and offered a reminder of the need to "think less about drugs and a great deal about whether we can prevent cancer."

The findings, he said, offer "yet another reason to encourage women to stop smoking." Dr. Sledge said he also found the reduced risk of colorectal cancer associated with moderate drinking "very interesting," but that more research would be needed.

The study by Dr. Land and her colleagues was funded by the National Cancer Institute. One of Dr. Land’s coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Early diagnoses of autism spectrum disorder are increasing in Massachusetts, particularly among boys, a study of 3,013 children who were enrolled in an early-intervention program has shown.

The study, published online May 16 in Pediatrics, linked data from state birth certificates and early-intervention program records. It showed that the incidence of autism spectrum disorders (ASDs) for children by age 3 increased 66% between 2001 and 2005, from 56 per 10,000, or 1 in 178, to 93 per 10,000, or 1 in 106. Early diagnoses increased among boys by more than 70%, from 88 per 10,000 children in 2001 to 151 per 10,000 in 2005. Diagnoses among girls, by contrast, increased 39% (doi: 10.1542/peds.2010-2943).

The findings, the investigators said, are broadly in keeping with national estimates published by the Centers for Disease Control and Prevention, which says an average of 1 in 110 U.S. children aged 8 years has Asperger’s disorder, autistic disorder, or pervasive developmental disorder, which all fall under the autism spectrum disorders.

For their research, Dr. Susan E. Manning and her colleagues matched data from a state ASD early-intervention program enrolling 3,013 children between 2001 and 2005 with birth certificate records, establishing successful links in 87.3% of cases.

Among the study’s additional findings was that ASD diagnoses were less common among infants of mothers 24 years old or younger and mothers whose first language was not English or who were foreign-born, reported Dr. Manning of the Massachusetts Department of Public Health, Boston, and the Centers for Disease Control and Prevention, Atlanta, and her colleagues, Odds of diagnosis were 4.5 (95% confidence interval, 4.1-5.0) times higher for boys than girls. Maternal age over 30 was associated with an elevated risk of diagnosis. Differences in rates of diagnosis among ethnic groups were narrower in 2005 than in 2001, the investigators found, and birth weight was the only variable seen differing significantly between boys and girls with ASDs (15.7% of girls had low birth weight, compared with 11% of boys), the investigators said (Pediatrics 2011;127:1043-51).

Symptoms of ASDs, particularly autism disorder, can be evident before 3 years, and "[m]ounting evidence suggests that early initiation of intensive intervention can improve developmental outcomes for children with ASDs," Dr. Manning and her colleagues wrote. Massachusetts established its early-intervention program in 1998 to provide specialty services to children with ASDs with the aim of improving outcomes. Altogether, 1 in every 129 Massachusetts children born between 2001 and 2005 was enrolled in early intervention with an ASD by the age of 36 months.

Among the limitations of the study is that confirmation of ASDs was not available for all children. "Thus our case definition might be overly inclusive," they wrote. "It is possible that ASDs might have been initially suspected because of the positive initial screen but subsequently ruled out. These factors would lead to an overestimation of early diagnosis of ASDs."

On the other hand, the findings might underestimate early diagnoses, the authors wrote, because some children who are on the spectrum might not participate in early-intervention programs, and would therefore be missed by the study. Nevertheless, the data are useful.

"Our analysis shows that linkage of early-intervention program data and population-based vital statistics data is useful for identifying trends and disparities in early ASD diagnoses," they wrote. "The results of this type of analysis can be used to increase clinician awareness of the early signs of ASDs and inform state early-intervention program efforts to anticipate future service demands and resources needed."

The study was financed by the Massachusetts Department of Public Health. None of its authors declared financial conflicts of interest except Karen Clements, Sc.D., who disclosed employment with i3 Innovus, a subsidiary of United Health Group that has a financial interest in the early diagnosis of autism.

Early diagnoses of autism spectrum disorder are increasing in Massachusetts, particularly among boys, a study of 3,013 children who were enrolled in an early-intervention program has shown.

The study, published online May 16 in Pediatrics, linked data from state birth certificates and early-intervention program records. It showed that the incidence of autism spectrum disorders (ASDs) for children by age 3 increased 66% between 2001 and 2005, from 56 per 10,000, or 1 in 178, to 93 per 10,000, or 1 in 106. Early diagnoses increased among boys by more than 70%, from 88 per 10,000 children in 2001 to 151 per 10,000 in 2005. Diagnoses among girls, by contrast, increased 39% (doi: 10.1542/peds.2010-2943).

The findings, the investigators said, are broadly in keeping with national estimates published by the Centers for Disease Control and Prevention, which says an average of 1 in 110 U.S. children aged 8 years has Asperger’s disorder, autistic disorder, or pervasive developmental disorder, which all fall under the autism spectrum disorders.

For their research, Dr. Susan E. Manning and her colleagues matched data from a state ASD early-intervention program enrolling 3,013 children between 2001 and 2005 with birth certificate records, establishing successful links in 87.3% of cases.

Among the study’s additional findings was that ASD diagnoses were less common among infants of mothers 24 years old or younger and mothers whose first language was not English or who were foreign-born, reported Dr. Manning of the Massachusetts Department of Public Health, Boston, and the Centers for Disease Control and Prevention, Atlanta, and her colleagues, Odds of diagnosis were 4.5 (95% confidence interval, 4.1-5.0) times higher for boys than girls. Maternal age over 30 was associated with an elevated risk of diagnosis. Differences in rates of diagnosis among ethnic groups were narrower in 2005 than in 2001, the investigators found, and birth weight was the only variable seen differing significantly between boys and girls with ASDs (15.7% of girls had low birth weight, compared with 11% of boys), the investigators said (Pediatrics 2011;127:1043-51).

Symptoms of ASDs, particularly autism disorder, can be evident before 3 years, and "[m]ounting evidence suggests that early initiation of intensive intervention can improve developmental outcomes for children with ASDs," Dr. Manning and her colleagues wrote. Massachusetts established its early-intervention program in 1998 to provide specialty services to children with ASDs with the aim of improving outcomes. Altogether, 1 in every 129 Massachusetts children born between 2001 and 2005 was enrolled in early intervention with an ASD by the age of 36 months.

Among the limitations of the study is that confirmation of ASDs was not available for all children. "Thus our case definition might be overly inclusive," they wrote. "It is possible that ASDs might have been initially suspected because of the positive initial screen but subsequently ruled out. These factors would lead to an overestimation of early diagnosis of ASDs."

On the other hand, the findings might underestimate early diagnoses, the authors wrote, because some children who are on the spectrum might not participate in early-intervention programs, and would therefore be missed by the study. Nevertheless, the data are useful.

"Our analysis shows that linkage of early-intervention program data and population-based vital statistics data is useful for identifying trends and disparities in early ASD diagnoses," they wrote. "The results of this type of analysis can be used to increase clinician awareness of the early signs of ASDs and inform state early-intervention program efforts to anticipate future service demands and resources needed."

The study was financed by the Massachusetts Department of Public Health. None of its authors declared financial conflicts of interest except Karen Clements, Sc.D., who disclosed employment with i3 Innovus, a subsidiary of United Health Group that has a financial interest in the early diagnosis of autism.

Early diagnoses of autism spectrum disorder are increasing in Massachusetts, particularly among boys, a study of 3,013 children who were enrolled in an early-intervention program has shown.

The study, published online May 16 in Pediatrics, linked data from state birth certificates and early-intervention program records. It showed that the incidence of autism spectrum disorders (ASDs) for children by age 3 increased 66% between 2001 and 2005, from 56 per 10,000, or 1 in 178, to 93 per 10,000, or 1 in 106. Early diagnoses increased among boys by more than 70%, from 88 per 10,000 children in 2001 to 151 per 10,000 in 2005. Diagnoses among girls, by contrast, increased 39% (doi: 10.1542/peds.2010-2943).

The findings, the investigators said, are broadly in keeping with national estimates published by the Centers for Disease Control and Prevention, which says an average of 1 in 110 U.S. children aged 8 years has Asperger’s disorder, autistic disorder, or pervasive developmental disorder, which all fall under the autism spectrum disorders.

For their research, Dr. Susan E. Manning and her colleagues matched data from a state ASD early-intervention program enrolling 3,013 children between 2001 and 2005 with birth certificate records, establishing successful links in 87.3% of cases.

Among the study’s additional findings was that ASD diagnoses were less common among infants of mothers 24 years old or younger and mothers whose first language was not English or who were foreign-born, reported Dr. Manning of the Massachusetts Department of Public Health, Boston, and the Centers for Disease Control and Prevention, Atlanta, and her colleagues, Odds of diagnosis were 4.5 (95% confidence interval, 4.1-5.0) times higher for boys than girls. Maternal age over 30 was associated with an elevated risk of diagnosis. Differences in rates of diagnosis among ethnic groups were narrower in 2005 than in 2001, the investigators found, and birth weight was the only variable seen differing significantly between boys and girls with ASDs (15.7% of girls had low birth weight, compared with 11% of boys), the investigators said (Pediatrics 2011;127:1043-51).

Symptoms of ASDs, particularly autism disorder, can be evident before 3 years, and "[m]ounting evidence suggests that early initiation of intensive intervention can improve developmental outcomes for children with ASDs," Dr. Manning and her colleagues wrote. Massachusetts established its early-intervention program in 1998 to provide specialty services to children with ASDs with the aim of improving outcomes. Altogether, 1 in every 129 Massachusetts children born between 2001 and 2005 was enrolled in early intervention with an ASD by the age of 36 months.

Among the limitations of the study is that confirmation of ASDs was not available for all children. "Thus our case definition might be overly inclusive," they wrote. "It is possible that ASDs might have been initially suspected because of the positive initial screen but subsequently ruled out. These factors would lead to an overestimation of early diagnosis of ASDs."

On the other hand, the findings might underestimate early diagnoses, the authors wrote, because some children who are on the spectrum might not participate in early-intervention programs, and would therefore be missed by the study. Nevertheless, the data are useful.

"Our analysis shows that linkage of early-intervention program data and population-based vital statistics data is useful for identifying trends and disparities in early ASD diagnoses," they wrote. "The results of this type of analysis can be used to increase clinician awareness of the early signs of ASDs and inform state early-intervention program efforts to anticipate future service demands and resources needed."

The study was financed by the Massachusetts Department of Public Health. None of its authors declared financial conflicts of interest except Karen Clements, Sc.D., who disclosed employment with i3 Innovus, a subsidiary of United Health Group that has a financial interest in the early diagnosis of autism.

The immunosuppressant drug pirfenidone was shown to modestly reduce lung function decline in patients with idiopathic pulmonary fibrosis, according to results from two phase III randomized, placebo-controlled trials.

The trials, enrolling 779 patients of both sexes aged 40-80 years at 110 sites worldwide, are the largest to date of pirfenidone in this patient group. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease that is generally fatal within 5 years, is classified as an orphan disease for which there are few treatment options.

The results, published online May 14 in the Lancet (doi:10.1016/S0140- 6736[11]60405-4), show a "clinically meaningful benefit" for people with IPF, wrote the investigators, led by Dr. Paul W. Noble, professor of medicine and chief of the pulmonary, allergy, and critical care medicine division at Duke University, Durham, N.C.

The trials, both sponsored by InterMune and similar in design, evaluated pirfenidone at different doses over a period of 72 weeks, with the primary end point being change from baseline in percentage predicted forced vital capacity (FVC). Secondary end points were progression-free survival and 6-minute walk test results.

In the first trial, 435 patients were randomized to receive pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo. In the second trial, 344 patients were randomized to pirfenidone 2,403 mg/day or placebo.

The first study showed an 8.4% decline in mean FVC in the pirfenidone group, compared with 12.4% in the placebo group after 72 weeks. In the second study, the difference between groups in FVC change at week 72 was not significant (9.0% for pirfenidone vs. 9.6% for placebo). However, the investigators noted, a "consistent pirfenidone effect was apparent until week 48 (P = .005) and in an analysis of all study time points (P = .007)" in the second study.

In a pooled analysis of both studies, the pirfenidone group saw fewer overall deaths (19, or 6%) than the placebo group (29, or 8%) and fewer deaths related to idiopathic pulmonary fibrosis (12, or 3%, with treatment, compared with 25, or 7%, with placebo). However, the trials were not powered to assess mortality. In both trials, the treatment groups saw significantly more adverse effects, including nausea, dyspepsia, vomiting, anorexia, photosensitivity, rash, and dizziness.

In a pooled analysis looking at FVC change, "pirfenidone reduced the proportion of patients with a 10% or more decrement by 30% compared with placebo," Dr. Noble and his colleagues wrote, noting that a 10% or greater decline is considered to be predictive of death in clinical practice. "Moreover, pirfenidone was associated with a 26% reduction in the risk of death or disease progression in analyses of progression-free survival, a 31% reduced mean decline in [6-minute walk test] at week 72, and a consistently favorable direction of effect on mortality, despite the trials not being powered to assess mortality," they wrote.

Dr. Noble and his colleagues acknowledged as limitations their enrollment of patients with mild to moderate disease and few comorbidities, meaning the results "cannot necessarily be generalized to the broader population of patients." Also, they noted, "the lack of adjustment for multiple statistical testing has the potential for overinterpretation of the results." Safety and tolerance beyond 72 weeks were not measured.

In an editorial accompanying the report, Dr. Demosthenes Bouros of Democritus University of Thrace in Alexandropolis, Greece, wrote that pirfenidone "could be appropriate in patients who are willing to accept possible adverse consequences even if expected benefits are small." Successful treatment of IPF "is likely to require a combination of therapies targeting several pathways involved in fibroproliferation," Dr. Bouros said (Lancet 2011 May 14 [doi:10.1016/S0140- 6736(11)60546-1]).

Pirfenidone has been licensed in Japan since 2008 for the treatment of IPF, and in February, the European Medicines Agency recommended marketing authorization throughout the European Union for pirfenidone, based in part on preliminary findings from the same two phase III trials.

Pirfenidone has not been approved by the U.S. Food and Drug Administration for patients with IPF. Earlier this month, despite a favorable 9-3 vote by its expert panel, the agency said it would need to see evidence from additional trials before approving pirfenidone.

Dr. Noble and his colleagues’ research was funded by InterMune, pirfenidone’s manufacturer. InterMune was involved with the study design, data collection, data analysis, writing, analysis, and maintenance of the data. Dr. Noble disclosed having served as an investigator for InterMune, and all but 2 of his 11 coauthors disclosed relationships with InterMune or are employees of InterMune. Dr. Bouros declared that he had no relevant financial disclosures.

The immunosuppressant drug pirfenidone was shown to modestly reduce lung function decline in patients with idiopathic pulmonary fibrosis, according to results from two phase III randomized, placebo-controlled trials.

The trials, enrolling 779 patients of both sexes aged 40-80 years at 110 sites worldwide, are the largest to date of pirfenidone in this patient group. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease that is generally fatal within 5 years, is classified as an orphan disease for which there are few treatment options.

The results, published online May 14 in the Lancet (doi:10.1016/S0140- 6736[11]60405-4), show a "clinically meaningful benefit" for people with IPF, wrote the investigators, led by Dr. Paul W. Noble, professor of medicine and chief of the pulmonary, allergy, and critical care medicine division at Duke University, Durham, N.C.

The trials, both sponsored by InterMune and similar in design, evaluated pirfenidone at different doses over a period of 72 weeks, with the primary end point being change from baseline in percentage predicted forced vital capacity (FVC). Secondary end points were progression-free survival and 6-minute walk test results.

In the first trial, 435 patients were randomized to receive pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo. In the second trial, 344 patients were randomized to pirfenidone 2,403 mg/day or placebo.

The first study showed an 8.4% decline in mean FVC in the pirfenidone group, compared with 12.4% in the placebo group after 72 weeks. In the second study, the difference between groups in FVC change at week 72 was not significant (9.0% for pirfenidone vs. 9.6% for placebo). However, the investigators noted, a "consistent pirfenidone effect was apparent until week 48 (P = .005) and in an analysis of all study time points (P = .007)" in the second study.

In a pooled analysis of both studies, the pirfenidone group saw fewer overall deaths (19, or 6%) than the placebo group (29, or 8%) and fewer deaths related to idiopathic pulmonary fibrosis (12, or 3%, with treatment, compared with 25, or 7%, with placebo). However, the trials were not powered to assess mortality. In both trials, the treatment groups saw significantly more adverse effects, including nausea, dyspepsia, vomiting, anorexia, photosensitivity, rash, and dizziness.

In a pooled analysis looking at FVC change, "pirfenidone reduced the proportion of patients with a 10% or more decrement by 30% compared with placebo," Dr. Noble and his colleagues wrote, noting that a 10% or greater decline is considered to be predictive of death in clinical practice. "Moreover, pirfenidone was associated with a 26% reduction in the risk of death or disease progression in analyses of progression-free survival, a 31% reduced mean decline in [6-minute walk test] at week 72, and a consistently favorable direction of effect on mortality, despite the trials not being powered to assess mortality," they wrote.

Dr. Noble and his colleagues acknowledged as limitations their enrollment of patients with mild to moderate disease and few comorbidities, meaning the results "cannot necessarily be generalized to the broader population of patients." Also, they noted, "the lack of adjustment for multiple statistical testing has the potential for overinterpretation of the results." Safety and tolerance beyond 72 weeks were not measured.

In an editorial accompanying the report, Dr. Demosthenes Bouros of Democritus University of Thrace in Alexandropolis, Greece, wrote that pirfenidone "could be appropriate in patients who are willing to accept possible adverse consequences even if expected benefits are small." Successful treatment of IPF "is likely to require a combination of therapies targeting several pathways involved in fibroproliferation," Dr. Bouros said (Lancet 2011 May 14 [doi:10.1016/S0140- 6736(11)60546-1]).

Pirfenidone has been licensed in Japan since 2008 for the treatment of IPF, and in February, the European Medicines Agency recommended marketing authorization throughout the European Union for pirfenidone, based in part on preliminary findings from the same two phase III trials.

Pirfenidone has not been approved by the U.S. Food and Drug Administration for patients with IPF. Earlier this month, despite a favorable 9-3 vote by its expert panel, the agency said it would need to see evidence from additional trials before approving pirfenidone.

Dr. Noble and his colleagues’ research was funded by InterMune, pirfenidone’s manufacturer. InterMune was involved with the study design, data collection, data analysis, writing, analysis, and maintenance of the data. Dr. Noble disclosed having served as an investigator for InterMune, and all but 2 of his 11 coauthors disclosed relationships with InterMune or are employees of InterMune. Dr. Bouros declared that he had no relevant financial disclosures.

The immunosuppressant drug pirfenidone was shown to modestly reduce lung function decline in patients with idiopathic pulmonary fibrosis, according to results from two phase III randomized, placebo-controlled trials.

The trials, enrolling 779 patients of both sexes aged 40-80 years at 110 sites worldwide, are the largest to date of pirfenidone in this patient group. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease that is generally fatal within 5 years, is classified as an orphan disease for which there are few treatment options.

The results, published online May 14 in the Lancet (doi:10.1016/S0140- 6736[11]60405-4), show a "clinically meaningful benefit" for people with IPF, wrote the investigators, led by Dr. Paul W. Noble, professor of medicine and chief of the pulmonary, allergy, and critical care medicine division at Duke University, Durham, N.C.

The trials, both sponsored by InterMune and similar in design, evaluated pirfenidone at different doses over a period of 72 weeks, with the primary end point being change from baseline in percentage predicted forced vital capacity (FVC). Secondary end points were progression-free survival and 6-minute walk test results.

In the first trial, 435 patients were randomized to receive pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo. In the second trial, 344 patients were randomized to pirfenidone 2,403 mg/day or placebo.

The first study showed an 8.4% decline in mean FVC in the pirfenidone group, compared with 12.4% in the placebo group after 72 weeks. In the second study, the difference between groups in FVC change at week 72 was not significant (9.0% for pirfenidone vs. 9.6% for placebo). However, the investigators noted, a "consistent pirfenidone effect was apparent until week 48 (P = .005) and in an analysis of all study time points (P = .007)" in the second study.

In a pooled analysis of both studies, the pirfenidone group saw fewer overall deaths (19, or 6%) than the placebo group (29, or 8%) and fewer deaths related to idiopathic pulmonary fibrosis (12, or 3%, with treatment, compared with 25, or 7%, with placebo). However, the trials were not powered to assess mortality. In both trials, the treatment groups saw significantly more adverse effects, including nausea, dyspepsia, vomiting, anorexia, photosensitivity, rash, and dizziness.

In a pooled analysis looking at FVC change, "pirfenidone reduced the proportion of patients with a 10% or more decrement by 30% compared with placebo," Dr. Noble and his colleagues wrote, noting that a 10% or greater decline is considered to be predictive of death in clinical practice. "Moreover, pirfenidone was associated with a 26% reduction in the risk of death or disease progression in analyses of progression-free survival, a 31% reduced mean decline in [6-minute walk test] at week 72, and a consistently favorable direction of effect on mortality, despite the trials not being powered to assess mortality," they wrote.

Dr. Noble and his colleagues acknowledged as limitations their enrollment of patients with mild to moderate disease and few comorbidities, meaning the results "cannot necessarily be generalized to the broader population of patients." Also, they noted, "the lack of adjustment for multiple statistical testing has the potential for overinterpretation of the results." Safety and tolerance beyond 72 weeks were not measured.

In an editorial accompanying the report, Dr. Demosthenes Bouros of Democritus University of Thrace in Alexandropolis, Greece, wrote that pirfenidone "could be appropriate in patients who are willing to accept possible adverse consequences even if expected benefits are small." Successful treatment of IPF "is likely to require a combination of therapies targeting several pathways involved in fibroproliferation," Dr. Bouros said (Lancet 2011 May 14 [doi:10.1016/S0140- 6736(11)60546-1]).

Pirfenidone has been licensed in Japan since 2008 for the treatment of IPF, and in February, the European Medicines Agency recommended marketing authorization throughout the European Union for pirfenidone, based in part on preliminary findings from the same two phase III trials.

Pirfenidone has not been approved by the U.S. Food and Drug Administration for patients with IPF. Earlier this month, despite a favorable 9-3 vote by its expert panel, the agency said it would need to see evidence from additional trials before approving pirfenidone.

Dr. Noble and his colleagues’ research was funded by InterMune, pirfenidone’s manufacturer. InterMune was involved with the study design, data collection, data analysis, writing, analysis, and maintenance of the data. Dr. Noble disclosed having served as an investigator for InterMune, and all but 2 of his 11 coauthors disclosed relationships with InterMune or are employees of InterMune. Dr. Bouros declared that he had no relevant financial disclosures.

The immunosuppressant drug pirfenidone was shown to modestly reduce lung function decline in patients with idiopathic pulmonary fibrosis, according to results from two phase III randomized, placebo-controlled trials.

The trials, enrolling 779 patients of both sexes aged 40-80 years at 110 sites worldwide, are the largest to date of pirfenidone in this patient group. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease that is generally fatal within 5 years, is classified as an orphan disease for which there are few treatment options.

The results, published online May 14 in the Lancet (doi:10.1016/S0140- 6736[11]60405-4), show a "clinically meaningful benefit" for people with IPF, wrote the investigators, led by Dr. Paul W. Noble, professor of medicine and chief of the pulmonary, allergy, and critical care medicine division at Duke University, Durham, N.C.

The trials, both sponsored by InterMune and similar in design, evaluated pirfenidone at different doses over a period of 72 weeks, with the primary end point being change from baseline in percentage predicted forced vital capacity (FVC). Secondary end points were progression-free survival and 6-minute walk test results.

In the first trial, 435 patients were randomized to receive pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo. In the second trial, 344 patients were randomized to pirfenidone 2,403 mg/day or placebo.

The first study showed an 8.4% decline in mean FVC in the pirfenidone group, compared with 12.4% in the placebo group after 72 weeks. In the second study, the difference between groups in FVC change at week 72 was not significant (9.0% for pirfenidone vs. 9.6% for placebo). However, the investigators noted, a "consistent pirfenidone effect was apparent until week 48 (P = .005) and in an analysis of all study time points (P = .007)" in the second study.

In a pooled analysis of both studies, the pirfenidone group saw fewer overall deaths (19, or 6%) than the placebo group (29, or 8%) and fewer deaths related to idiopathic pulmonary fibrosis (12, or 3%, with treatment, compared with 25, or 7%, with placebo). However, the trials were not powered to assess mortality. In both trials, the treatment groups saw significantly more adverse effects, including nausea, dyspepsia, vomiting, anorexia, photosensitivity, rash, and dizziness.

In a pooled analysis looking at FVC change, "pirfenidone reduced the proportion of patients with a 10% or more decrement by 30% compared with placebo," Dr. Noble and his colleagues wrote, noting that a 10% or greater decline is considered to be predictive of death in clinical practice. "Moreover, pirfenidone was associated with a 26% reduction in the risk of death or disease progression in analyses of progression-free survival, a 31% reduced mean decline in [6-minute walk test] at week 72, and a consistently favorable direction of effect on mortality, despite the trials not being powered to assess mortality," they wrote.

Dr. Noble and his colleagues acknowledged as limitations their enrollment of patients with mild to moderate disease and few comorbidities, meaning the results "cannot necessarily be generalized to the broader population of patients." Also, they noted, "the lack of adjustment for multiple statistical testing has the potential for overinterpretation of the results." Safety and tolerance beyond 72 weeks were not measured.

In an editorial accompanying the report, Dr. Demosthenes Bouros of Democritus University of Thrace in Alexandropolis, Greece, wrote that pirfenidone "could be appropriate in patients who are willing to accept possible adverse consequences even if expected benefits are small." Successful treatment of IPF "is likely to require a combination of therapies targeting several pathways involved in fibroproliferation," Dr. Bouros said (Lancet 2011 May 14 [doi:10.1016/S0140- 6736(11)60546-1]).

Pirfenidone has been licensed in Japan since 2008 for the treatment of IPF, and in February, the European Medicines Agency recommended marketing authorization throughout the European Union for pirfenidone, based in part on preliminary findings from the same two phase III trials.

Pirfenidone has not been approved by the U.S. Food and Drug Administration for patients with IPF. Earlier this month, despite a favorable 9-3 vote by its expert panel, the agency said it would need to see evidence from additional trials before approving pirfenidone.

Dr. Noble and his colleagues’ research was funded by InterMune, pirfenidone’s manufacturer. InterMune was involved with the study design, data collection, data analysis, writing, analysis, and maintenance of the data. Dr. Noble disclosed having served as an investigator for InterMune, and all but 2 of his 11 coauthors disclosed relationships with InterMune or are employees of InterMune. Dr. Bouros declared that he had no relevant financial disclosures.

The immunosuppressant drug pirfenidone was shown to modestly reduce lung function decline in patients with idiopathic pulmonary fibrosis, according to results from two phase III randomized, placebo-controlled trials.

The trials, enrolling 779 patients of both sexes aged 40-80 years at 110 sites worldwide, are the largest to date of pirfenidone in this patient group. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease that is generally fatal within 5 years, is classified as an orphan disease for which there are few treatment options.

The results, published online May 14 in the Lancet (doi:10.1016/S0140- 6736[11]60405-4), show a "clinically meaningful benefit" for people with IPF, wrote the investigators, led by Dr. Paul W. Noble, professor of medicine and chief of the pulmonary, allergy, and critical care medicine division at Duke University, Durham, N.C.

The trials, both sponsored by InterMune and similar in design, evaluated pirfenidone at different doses over a period of 72 weeks, with the primary end point being change from baseline in percentage predicted forced vital capacity (FVC). Secondary end points were progression-free survival and 6-minute walk test results.

In the first trial, 435 patients were randomized to receive pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo. In the second trial, 344 patients were randomized to pirfenidone 2,403 mg/day or placebo.

The first study showed an 8.4% decline in mean FVC in the pirfenidone group, compared with 12.4% in the placebo group after 72 weeks. In the second study, the difference between groups in FVC change at week 72 was not significant (9.0% for pirfenidone vs. 9.6% for placebo). However, the investigators noted, a "consistent pirfenidone effect was apparent until week 48 (P = .005) and in an analysis of all study time points (P = .007)" in the second study.

In a pooled analysis of both studies, the pirfenidone group saw fewer overall deaths (19, or 6%) than the placebo group (29, or 8%) and fewer deaths related to idiopathic pulmonary fibrosis (12, or 3%, with treatment, compared with 25, or 7%, with placebo). However, the trials were not powered to assess mortality. In both trials, the treatment groups saw significantly more adverse effects, including nausea, dyspepsia, vomiting, anorexia, photosensitivity, rash, and dizziness.

In a pooled analysis looking at FVC change, "pirfenidone reduced the proportion of patients with a 10% or more decrement by 30% compared with placebo," Dr. Noble and his colleagues wrote, noting that a 10% or greater decline is considered to be predictive of death in clinical practice. "Moreover, pirfenidone was associated with a 26% reduction in the risk of death or disease progression in analyses of progression-free survival, a 31% reduced mean decline in [6-minute walk test] at week 72, and a consistently favorable direction of effect on mortality, despite the trials not being powered to assess mortality," they wrote.

Dr. Noble and his colleagues acknowledged as limitations their enrollment of patients with mild to moderate disease and few comorbidities, meaning the results "cannot necessarily be generalized to the broader population of patients." Also, they noted, "the lack of adjustment for multiple statistical testing has the potential for overinterpretation of the results." Safety and tolerance beyond 72 weeks were not measured.

In an editorial accompanying the report, Dr. Demosthenes Bouros of Democritus University of Thrace in Alexandropolis, Greece, wrote that pirfenidone "could be appropriate in patients who are willing to accept possible adverse consequences even if expected benefits are small." Successful treatment of IPF "is likely to require a combination of therapies targeting several pathways involved in fibroproliferation," Dr. Bouros said (Lancet 2011 May 14 [doi:10.1016/S0140- 6736(11)60546-1]).

Pirfenidone has been licensed in Japan since 2008 for the treatment of IPF, and in February, the European Medicines Agency recommended marketing authorization throughout the European Union for pirfenidone, based in part on preliminary findings from the same two phase III trials.

Pirfenidone has not been approved by the U.S. Food and Drug Administration for patients with IPF. Earlier this month, despite a favorable 9-3 vote by its expert panel, the agency said it would need to see evidence from additional trials before approving pirfenidone.

Dr. Noble and his colleagues’ research was funded by InterMune, pirfenidone’s manufacturer. InterMune was involved with the study design, data collection, data analysis, writing, analysis, and maintenance of the data. Dr. Noble disclosed having served as an investigator for InterMune, and all but 2 of his 11 coauthors disclosed relationships with InterMune or are employees of InterMune. Dr. Bouros declared that he had no relevant financial disclosures.

The immunosuppressant drug pirfenidone was shown to modestly reduce lung function decline in patients with idiopathic pulmonary fibrosis, according to results from two phase III randomized, placebo-controlled trials.

The trials, enrolling 779 patients of both sexes aged 40-80 years at 110 sites worldwide, are the largest to date of pirfenidone in this patient group. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease that is generally fatal within 5 years, is classified as an orphan disease for which there are few treatment options.

The results, published online May 14 in the Lancet (doi:10.1016/S0140- 6736[11]60405-4), show a "clinically meaningful benefit" for people with IPF, wrote the investigators, led by Dr. Paul W. Noble, professor of medicine and chief of the pulmonary, allergy, and critical care medicine division at Duke University, Durham, N.C.

The trials, both sponsored by InterMune and similar in design, evaluated pirfenidone at different doses over a period of 72 weeks, with the primary end point being change from baseline in percentage predicted forced vital capacity (FVC). Secondary end points were progression-free survival and 6-minute walk test results.

In the first trial, 435 patients were randomized to receive pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo. In the second trial, 344 patients were randomized to pirfenidone 2,403 mg/day or placebo.

The first study showed an 8.4% decline in mean FVC in the pirfenidone group, compared with 12.4% in the placebo group after 72 weeks. In the second study, the difference between groups in FVC change at week 72 was not significant (9.0% for pirfenidone vs. 9.6% for placebo). However, the investigators noted, a "consistent pirfenidone effect was apparent until week 48 (P = .005) and in an analysis of all study time points (P = .007)" in the second study.

In a pooled analysis of both studies, the pirfenidone group saw fewer overall deaths (19, or 6%) than the placebo group (29, or 8%) and fewer deaths related to idiopathic pulmonary fibrosis (12, or 3%, with treatment, compared with 25, or 7%, with placebo). However, the trials were not powered to assess mortality. In both trials, the treatment groups saw significantly more adverse effects, including nausea, dyspepsia, vomiting, anorexia, photosensitivity, rash, and dizziness.

In a pooled analysis looking at FVC change, "pirfenidone reduced the proportion of patients with a 10% or more decrement by 30% compared with placebo," Dr. Noble and his colleagues wrote, noting that a 10% or greater decline is considered to be predictive of death in clinical practice. "Moreover, pirfenidone was associated with a 26% reduction in the risk of death or disease progression in analyses of progression-free survival, a 31% reduced mean decline in [6-minute walk test] at week 72, and a consistently favorable direction of effect on mortality, despite the trials not being powered to assess mortality," they wrote.

Dr. Noble and his colleagues acknowledged as limitations their enrollment of patients with mild to moderate disease and few comorbidities, meaning the results "cannot necessarily be generalized to the broader population of patients." Also, they noted, "the lack of adjustment for multiple statistical testing has the potential for overinterpretation of the results." Safety and tolerance beyond 72 weeks were not measured.

In an editorial accompanying the report, Dr. Demosthenes Bouros of Democritus University of Thrace in Alexandropolis, Greece, wrote that pirfenidone "could be appropriate in patients who are willing to accept possible adverse consequences even if expected benefits are small." Successful treatment of IPF "is likely to require a combination of therapies targeting several pathways involved in fibroproliferation," Dr. Bouros said (Lancet 2011 May 14 [doi:10.1016/S0140- 6736(11)60546-1]).

Pirfenidone has been licensed in Japan since 2008 for the treatment of IPF, and in February, the European Medicines Agency recommended marketing authorization throughout the European Union for pirfenidone, based in part on preliminary findings from the same two phase III trials.

Pirfenidone has not been approved by the U.S. Food and Drug Administration for patients with IPF. Earlier this month, despite a favorable 9-3 vote by its expert panel, the agency said it would need to see evidence from additional trials before approving pirfenidone.

Dr. Noble and his colleagues’ research was funded by InterMune, pirfenidone’s manufacturer. InterMune was involved with the study design, data collection, data analysis, writing, analysis, and maintenance of the data. Dr. Noble disclosed having served as an investigator for InterMune, and all but 2 of his 11 coauthors disclosed relationships with InterMune or are employees of InterMune. Dr. Bouros declared that he had no relevant financial disclosures.

Early diagnoses of autism spectrum disorder are increasing in Massachusetts, particularly among boys, a study of 3,013 children who were enrolled in an early-intervention program has shown.

The study, published online May 16 in Pediatrics, linked data from state birth certificates and early-intervention program records. It showed that the incidence of autism spectrum disorders (ASDs) for children by age 3 increased 66% between 2001 and 2005, from 56 per 10,000, or 1 in 178, to 93 per 10,000, or 1 in 106. Early diagnoses increased among boys by more than 70%, from 88 per 10,000 children in 2001 to 151 per 10,000 in 2005. Diagnoses among girls, by contrast, increased 39% (doi: 10.1542/peds.2010-2943).

The findings, the investigators said, are broadly in keeping with national estimates published by the Centers for Disease Control and Prevention, which says an average of 1 in 110 U.S. children aged 8 years has Asperger’s disorder, autistic disorder, or pervasive developmental disorder, which all fall under the autism spectrum disorders.

For their research, Dr. Susan E. Manning and her colleagues matched data from a state ASD early-intervention program enrolling 3,013 children between 2001 and 2005 with birth certificate records, establishing successful links in 87.3% of cases.

Among the study’s additional findings was that ASD diagnoses were less common among infants of mothers 24 years old or younger and mothers whose first language was not English or who were foreign-born, reported Dr. Manning of the Massachusetts Department of Public Health, Boston, and the Centers for Disease Control and Prevention, Atlanta, and her colleagues, Odds of diagnosis were 4.5 (95% confidence interval, 4.1-5.0) times higher for boys than girls. Maternal age over 30 was associated with an elevated risk of diagnosis. Differences in rates of diagnosis among ethnic groups were narrower in 2005 than in 2001, the investigators found, and birth weight was the only variable seen differing significantly between boys and girls with ASDs (15.7% of girls had low birth weight, compared with 11% of boys), the investigators said (Pediatrics 2011;127:1043-51).

Symptoms of ASDs, particularly autism disorder, can be evident before 3 years, and "[m]ounting evidence suggests that early initiation of intensive intervention can improve developmental outcomes for children with ASDs," Dr. Manning and her colleagues wrote. Massachusetts established its early-intervention program in 1998 to provide specialty services to children with ASDs with the aim of improving outcomes. Altogether, 1 in every 129 Massachusetts children born between 2001 and 2005 was enrolled in early intervention with an ASD by the age of 36 months.

Among the limitations of the study is that confirmation of ASDs was not available for all children. "Thus our case definition might be overly inclusive," they wrote. "It is possible that ASDs might have been initially suspected because of the positive initial screen but subsequently ruled out. These factors would lead to an overestimation of early diagnosis of ASDs."

On the other hand, the findings might underestimate early diagnoses, the authors wrote, because some children who are on the spectrum might not participate in early-intervention programs, and would therefore be missed by the study. Nevertheless, the data are useful.

"Our analysis shows that linkage of early-intervention program data and population-based vital statistics data is useful for identifying trends and disparities in early ASD diagnoses," they wrote. "The results of this type of analysis can be used to increase clinician awareness of the early signs of ASDs and inform state early-intervention program efforts to anticipate future service demands and resources needed."

The study was financed by the Massachusetts Department of Public Health. None of its authors declared financial conflicts of interest except Karen Clements, Sc.D., who disclosed employment with i3 Innovus, a subsidiary of United Health Group that has a financial interest in the early diagnosis of autism.

Early diagnoses of autism spectrum disorder are increasing in Massachusetts, particularly among boys, a study of 3,013 children who were enrolled in an early-intervention program has shown.

The study, published online May 16 in Pediatrics, linked data from state birth certificates and early-intervention program records. It showed that the incidence of autism spectrum disorders (ASDs) for children by age 3 increased 66% between 2001 and 2005, from 56 per 10,000, or 1 in 178, to 93 per 10,000, or 1 in 106. Early diagnoses increased among boys by more than 70%, from 88 per 10,000 children in 2001 to 151 per 10,000 in 2005. Diagnoses among girls, by contrast, increased 39% (doi: 10.1542/peds.2010-2943).

The findings, the investigators said, are broadly in keeping with national estimates published by the Centers for Disease Control and Prevention, which says an average of 1 in 110 U.S. children aged 8 years has Asperger’s disorder, autistic disorder, or pervasive developmental disorder, which all fall under the autism spectrum disorders.

For their research, Dr. Susan E. Manning and her colleagues matched data from a state ASD early-intervention program enrolling 3,013 children between 2001 and 2005 with birth certificate records, establishing successful links in 87.3% of cases.

Among the study’s additional findings was that ASD diagnoses were less common among infants of mothers 24 years old or younger and mothers whose first language was not English or who were foreign-born, reported Dr. Manning of the Massachusetts Department of Public Health, Boston, and the Centers for Disease Control and Prevention, Atlanta, and her colleagues, Odds of diagnosis were 4.5 (95% confidence interval, 4.1-5.0) times higher for boys than girls. Maternal age over 30 was associated with an elevated risk of diagnosis. Differences in rates of diagnosis among ethnic groups were narrower in 2005 than in 2001, the investigators found, and birth weight was the only variable seen differing significantly between boys and girls with ASDs (15.7% of girls had low birth weight, compared with 11% of boys), the investigators said (Pediatrics 2011;127:1043-51).

Symptoms of ASDs, particularly autism disorder, can be evident before 3 years, and "[m]ounting evidence suggests that early initiation of intensive intervention can improve developmental outcomes for children with ASDs," Dr. Manning and her colleagues wrote. Massachusetts established its early-intervention program in 1998 to provide specialty services to children with ASDs with the aim of improving outcomes. Altogether, 1 in every 129 Massachusetts children born between 2001 and 2005 was enrolled in early intervention with an ASD by the age of 36 months.

Among the limitations of the study is that confirmation of ASDs was not available for all children. "Thus our case definition might be overly inclusive," they wrote. "It is possible that ASDs might have been initially suspected because of the positive initial screen but subsequently ruled out. These factors would lead to an overestimation of early diagnosis of ASDs."

On the other hand, the findings might underestimate early diagnoses, the authors wrote, because some children who are on the spectrum might not participate in early-intervention programs, and would therefore be missed by the study. Nevertheless, the data are useful.

"Our analysis shows that linkage of early-intervention program data and population-based vital statistics data is useful for identifying trends and disparities in early ASD diagnoses," they wrote. "The results of this type of analysis can be used to increase clinician awareness of the early signs of ASDs and inform state early-intervention program efforts to anticipate future service demands and resources needed."

The study was financed by the Massachusetts Department of Public Health. None of its authors declared financial conflicts of interest except Karen Clements, Sc.D., who disclosed employment with i3 Innovus, a subsidiary of United Health Group that has a financial interest in the early diagnosis of autism.

Early diagnoses of autism spectrum disorder are increasing in Massachusetts, particularly among boys, a study of 3,013 children who were enrolled in an early-intervention program has shown.

The study, published online May 16 in Pediatrics, linked data from state birth certificates and early-intervention program records. It showed that the incidence of autism spectrum disorders (ASDs) for children by age 3 increased 66% between 2001 and 2005, from 56 per 10,000, or 1 in 178, to 93 per 10,000, or 1 in 106. Early diagnoses increased among boys by more than 70%, from 88 per 10,000 children in 2001 to 151 per 10,000 in 2005. Diagnoses among girls, by contrast, increased 39% (doi: 10.1542/peds.2010-2943).

The findings, the investigators said, are broadly in keeping with national estimates published by the Centers for Disease Control and Prevention, which says an average of 1 in 110 U.S. children aged 8 years has Asperger’s disorder, autistic disorder, or pervasive developmental disorder, which all fall under the autism spectrum disorders.

For their research, Dr. Susan E. Manning and her colleagues matched data from a state ASD early-intervention program enrolling 3,013 children between 2001 and 2005 with birth certificate records, establishing successful links in 87.3% of cases.

Among the study’s additional findings was that ASD diagnoses were less common among infants of mothers 24 years old or younger and mothers whose first language was not English or who were foreign-born, reported Dr. Manning of the Massachusetts Department of Public Health, Boston, and the Centers for Disease Control and Prevention, Atlanta, and her colleagues, Odds of diagnosis were 4.5 (95% confidence interval, 4.1-5.0) times higher for boys than girls. Maternal age over 30 was associated with an elevated risk of diagnosis. Differences in rates of diagnosis among ethnic groups were narrower in 2005 than in 2001, the investigators found, and birth weight was the only variable seen differing significantly between boys and girls with ASDs (15.7% of girls had low birth weight, compared with 11% of boys), the investigators said (Pediatrics 2011;127:1043-51).

Symptoms of ASDs, particularly autism disorder, can be evident before 3 years, and "[m]ounting evidence suggests that early initiation of intensive intervention can improve developmental outcomes for children with ASDs," Dr. Manning and her colleagues wrote. Massachusetts established its early-intervention program in 1998 to provide specialty services to children with ASDs with the aim of improving outcomes. Altogether, 1 in every 129 Massachusetts children born between 2001 and 2005 was enrolled in early intervention with an ASD by the age of 36 months.

Among the limitations of the study is that confirmation of ASDs was not available for all children. "Thus our case definition might be overly inclusive," they wrote. "It is possible that ASDs might have been initially suspected because of the positive initial screen but subsequently ruled out. These factors would lead to an overestimation of early diagnosis of ASDs."

On the other hand, the findings might underestimate early diagnoses, the authors wrote, because some children who are on the spectrum might not participate in early-intervention programs, and would therefore be missed by the study. Nevertheless, the data are useful.

"Our analysis shows that linkage of early-intervention program data and population-based vital statistics data is useful for identifying trends and disparities in early ASD diagnoses," they wrote. "The results of this type of analysis can be used to increase clinician awareness of the early signs of ASDs and inform state early-intervention program efforts to anticipate future service demands and resources needed."

The study was financed by the Massachusetts Department of Public Health. None of its authors declared financial conflicts of interest except Karen Clements, Sc.D., who disclosed employment with i3 Innovus, a subsidiary of United Health Group that has a financial interest in the early diagnosis of autism.