Frail Elderly Benefit From Post-Op Temozolomide for Glioblastoma

MONTREAL – Elderly patients with newly diagnosed glioblastoma and poor Karnofsky performance scores can benefit from postsurgical chemotherapy with temozolomide, based on the results of a single-arm study in 70 patients.

Not only were most patients able to withstand treatment-related toxicity, but survival rates and performance status appeared to improve with treatment, Dr. Jamie Gállego Pérez-Larraya reported at the annual meeting of the Society for Neuro-Oncology.

Median overall survival, the primary end point, reached 25 weeks, with a 6-month overall survival rate of 44.3% and a 12-month rate of 11.4%, said Dr. Pérez-Larraya of the Hôpital Pitié-Salpêtrière in Paris. Median progression-free survival, a secondary end point, was 16 weeks, with a 6-month rate of 30%.

"These data compare favorably to the 17-week median survival reported in elderly patients with glioblastoma and good performance treated only with palliative care," he said.

The trial from ANOCEF (Association des Neuro-Oncologues d'Expression Française) enrolled 70 patients aged 70 and up (median age, 77 years), with newly diagnosed and histologically confirmed glioblastoma, a median Karnofsky performance score of 60, and no previous radiotherapy or chemotherapy for the brain tumor. Most (92%) had undergone biopsy of their tumor; five patients had received a partial resection, and one had a complete resection.

Temozolomide chemotherapy started at 150 mg/m2 for 5 consecutive days every 28 days, with dose escalation up to 200 mg/m2 in the absence of grade 3 or 4 toxicities for a maximum of 12 cycles, or until disease progression. Patients who progressed received supportive care; no radiotherapy was given.

Quality of life (QOL) and cognitive function outcomes were measured by EORTC (European Organisation for Research and Treatment of Cancer) questionnaires (QLQ-C30 and QLQ-BN20), and the Mini-Mental State Examination (MMSE). The study showed significant improvements on the global QOL scale and most functioning domains, with no decline in any domain, he said.

A third of the cohort improved their Karnofsky performance scores by at least 10 points, and 26% achieved a score of 70 or greater. "This is clinically significant because it means they became capable of self-care," he noted.

Treatment with temozolomide was "generally well tolerated," Dr. Pérez-Larraya reported. Twelve patients, (17%) had grade 3 or 4 thrombocytopenia or neutropenia, but these toxicities did not lead to dose delays or dose reductions.

All of the cohort had died by the time of presentation – 87% as a result of disease progression, and 13% from other causes, with no deaths due to toxicity.

"Until a few years ago the treatment of these patients received little attention mainly because of their poor expected survival, but also because of the fear of treatment-related toxicity," said Dr. Pérez-Larraya.

Now patients with good performance scores can be treated with postsurgical radiotherapy, which has been shown to prolong survival from 17 weeks to 29 weeks without causing deterioration in quality of life or cognitive function (N. Engl. J. Med. 2007;356:1527-35), he said. But the management of patients with poor scores has never been studied and remains uncertain.

"Radiotherapy requires many trips to the hospital, and increasing fatigue makes this difficult for these severely impaired patients with such a short expected survival. As a result, these patients frequently receive only supportive care," he explained.

"These results suggest that treatment with temozolomide in elderly patients with glioblastoma and poor performance score has an acceptable safety profile; is associated with an improvement in functional status in one-third of cases, as well as quality of life before progression; and seems to increase survival as compared to supportive care alone," Dr. Pérez-Larraya concluded.

He reported having no relevant financial disclosures.

MONTREAL – Elderly patients with newly diagnosed glioblastoma and poor Karnofsky performance scores can benefit from postsurgical chemotherapy with temozolomide, based on the results of a single-arm study in 70 patients.

Not only were most patients able to withstand treatment-related toxicity, but survival rates and performance status appeared to improve with treatment, Dr. Jamie Gállego Pérez-Larraya reported at the annual meeting of the Society for Neuro-Oncology.

Median overall survival, the primary end point, reached 25 weeks, with a 6-month overall survival rate of 44.3% and a 12-month rate of 11.4%, said Dr. Pérez-Larraya of the Hôpital Pitié-Salpêtrière in Paris. Median progression-free survival, a secondary end point, was 16 weeks, with a 6-month rate of 30%.

"These data compare favorably to the 17-week median survival reported in elderly patients with glioblastoma and good performance treated only with palliative care," he said.

The trial from ANOCEF (Association des Neuro-Oncologues d'Expression Française) enrolled 70 patients aged 70 and up (median age, 77 years), with newly diagnosed and histologically confirmed glioblastoma, a median Karnofsky performance score of 60, and no previous radiotherapy or chemotherapy for the brain tumor. Most (92%) had undergone biopsy of their tumor; five patients had received a partial resection, and one had a complete resection.

Temozolomide chemotherapy started at 150 mg/m2 for 5 consecutive days every 28 days, with dose escalation up to 200 mg/m2 in the absence of grade 3 or 4 toxicities for a maximum of 12 cycles, or until disease progression. Patients who progressed received supportive care; no radiotherapy was given.

Quality of life (QOL) and cognitive function outcomes were measured by EORTC (European Organisation for Research and Treatment of Cancer) questionnaires (QLQ-C30 and QLQ-BN20), and the Mini-Mental State Examination (MMSE). The study showed significant improvements on the global QOL scale and most functioning domains, with no decline in any domain, he said.

A third of the cohort improved their Karnofsky performance scores by at least 10 points, and 26% achieved a score of 70 or greater. "This is clinically significant because it means they became capable of self-care," he noted.

Treatment with temozolomide was "generally well tolerated," Dr. Pérez-Larraya reported. Twelve patients, (17%) had grade 3 or 4 thrombocytopenia or neutropenia, but these toxicities did not lead to dose delays or dose reductions.

All of the cohort had died by the time of presentation – 87% as a result of disease progression, and 13% from other causes, with no deaths due to toxicity.

"Until a few years ago the treatment of these patients received little attention mainly because of their poor expected survival, but also because of the fear of treatment-related toxicity," said Dr. Pérez-Larraya.

Now patients with good performance scores can be treated with postsurgical radiotherapy, which has been shown to prolong survival from 17 weeks to 29 weeks without causing deterioration in quality of life or cognitive function (N. Engl. J. Med. 2007;356:1527-35), he said. But the management of patients with poor scores has never been studied and remains uncertain.

"Radiotherapy requires many trips to the hospital, and increasing fatigue makes this difficult for these severely impaired patients with such a short expected survival. As a result, these patients frequently receive only supportive care," he explained.

"These results suggest that treatment with temozolomide in elderly patients with glioblastoma and poor performance score has an acceptable safety profile; is associated with an improvement in functional status in one-third of cases, as well as quality of life before progression; and seems to increase survival as compared to supportive care alone," Dr. Pérez-Larraya concluded.

He reported having no relevant financial disclosures.

MONTREAL – Elderly patients with newly diagnosed glioblastoma and poor Karnofsky performance scores can benefit from postsurgical chemotherapy with temozolomide, based on the results of a single-arm study in 70 patients.

Not only were most patients able to withstand treatment-related toxicity, but survival rates and performance status appeared to improve with treatment, Dr. Jamie Gállego Pérez-Larraya reported at the annual meeting of the Society for Neuro-Oncology.

Median overall survival, the primary end point, reached 25 weeks, with a 6-month overall survival rate of 44.3% and a 12-month rate of 11.4%, said Dr. Pérez-Larraya of the Hôpital Pitié-Salpêtrière in Paris. Median progression-free survival, a secondary end point, was 16 weeks, with a 6-month rate of 30%.

"These data compare favorably to the 17-week median survival reported in elderly patients with glioblastoma and good performance treated only with palliative care," he said.

The trial from ANOCEF (Association des Neuro-Oncologues d'Expression Française) enrolled 70 patients aged 70 and up (median age, 77 years), with newly diagnosed and histologically confirmed glioblastoma, a median Karnofsky performance score of 60, and no previous radiotherapy or chemotherapy for the brain tumor. Most (92%) had undergone biopsy of their tumor; five patients had received a partial resection, and one had a complete resection.

Temozolomide chemotherapy started at 150 mg/m2 for 5 consecutive days every 28 days, with dose escalation up to 200 mg/m2 in the absence of grade 3 or 4 toxicities for a maximum of 12 cycles, or until disease progression. Patients who progressed received supportive care; no radiotherapy was given.

Quality of life (QOL) and cognitive function outcomes were measured by EORTC (European Organisation for Research and Treatment of Cancer) questionnaires (QLQ-C30 and QLQ-BN20), and the Mini-Mental State Examination (MMSE). The study showed significant improvements on the global QOL scale and most functioning domains, with no decline in any domain, he said.

A third of the cohort improved their Karnofsky performance scores by at least 10 points, and 26% achieved a score of 70 or greater. "This is clinically significant because it means they became capable of self-care," he noted.

Treatment with temozolomide was "generally well tolerated," Dr. Pérez-Larraya reported. Twelve patients, (17%) had grade 3 or 4 thrombocytopenia or neutropenia, but these toxicities did not lead to dose delays or dose reductions.

All of the cohort had died by the time of presentation – 87% as a result of disease progression, and 13% from other causes, with no deaths due to toxicity.

"Until a few years ago the treatment of these patients received little attention mainly because of their poor expected survival, but also because of the fear of treatment-related toxicity," said Dr. Pérez-Larraya.

Now patients with good performance scores can be treated with postsurgical radiotherapy, which has been shown to prolong survival from 17 weeks to 29 weeks without causing deterioration in quality of life or cognitive function (N. Engl. J. Med. 2007;356:1527-35), he said. But the management of patients with poor scores has never been studied and remains uncertain.

"Radiotherapy requires many trips to the hospital, and increasing fatigue makes this difficult for these severely impaired patients with such a short expected survival. As a result, these patients frequently receive only supportive care," he explained.

"These results suggest that treatment with temozolomide in elderly patients with glioblastoma and poor performance score has an acceptable safety profile; is associated with an improvement in functional status in one-third of cases, as well as quality of life before progression; and seems to increase survival as compared to supportive care alone," Dr. Pérez-Larraya concluded.

He reported having no relevant financial disclosures.