Temozolomide, Wafers Added To CNS Cancer Guidelines

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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