Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma

Jun 11, 2009Cancer

Temozolomide with radiotherapy in older glioblastoma patients linked to MGMT gene methylation

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Abstract

A total of 58 elderly glioblastoma patients were treated with radiotherapy and temozolomide, achieving a median survival time of 13.7 months.

Concomitant and adjuvant temozolomide combined with radiotherapy is associated with improved overall and progression-free survival compared to radiotherapy alone.
The median progression-free survival was 9.5 months, indicating a potential benefit in treatment efficacy.
Mental status deterioration of grade 3-4 occurred in 25% of patients, suggesting significant toxicity linked to the treatment regimen.
Leukoencephalopathy was diagnosed in 10% of patients, highlighting a risk of neurological side effects.
MGMT promoter methylation status was present in 43% of patients, which may correlate with treatment outcomes.

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BACKGROUND: A recent randomized study conducted on newly diagnosed glioblastoma (GBM) patients demonstrated that concomitant and adjuvant temozolomide added to standard radiotherapy had a survival advantage compared with radiotherapy alone. The overall survival benefit of this aggressive treatment, however, was attenuated in older or poor performance status patients. The aim of the present study was to verify the activity and the toxicity of temozolomide administration concurrent and adjuvant to radiotherapy as first-line treatment for elderly GBM patients, and to explore correlations between clinical outcome and O6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status.

METHODS: Newly diagnosed GBM patients>or=65 years were considered eligible. Treatment comprised radiotherapy (60 Gy in 30 fractions over 6 weeks) plus continuous daily temozolomide (75 mg/m2/day), followed by 12 maintenance temozolomide cycles (150 mg/m2 once a day for 5 consecutive days every 28 days) if MRI showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression.

RESULTS: A total of 58 patients (34 males; median age, 68 years; range, 65-82 years) were enrolled. Sixteen patients (43%) presented MGMT promoter methylated and 21 unmethylated (57%) status. The median progression-free survival and median survival time (MST) were 9.5 months (95% confidence interval [CI], 8.6-10.5) and 13.7 months (95% CI, 10-17.3 months), respectively. Mental status deterioration grade 3-4 was detected in 25% of patients. Leukoencephalopathy was diagnosed in 10% of patients.

CONCLUSIONS: The overall and progression-free survival of patients given concomitant and adjuvant temozolomide are greater than in those given radiotherapy alone; however, this regimen incurs a greater deterioration in mental status. Further randomized trials should, therefore, be conducted to investigate the efficacy and against the toxicity of this regimen as first-line therapy in patients with GBM.

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Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma

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