Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma

Abstract

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 ≥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. Cancer 2009. © 2009 American Cancer Society.

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

“…43 In addition, the observation that 74% of patients with glioblastoma who survive for >5 years have MGMT promoter methylation-as opposed to <50% in an unselected population of glioblastoma patients-also underlines the prognostic value of MGMT status. 44 Nevertheless, long-term survival can be observed even in the absence of MGMT promoter methylation, indicating that MGMT promoter methylation is only one aspect of a very complex biological system.…”

Controversies in the Adjuvant Therapy of High-Grade Gliomas

“…Although the reported rates of acute toxicities do not seem much different between younger and older patients, the elderly may have a higher rate of delayed cognitive decline [25]. There are data suggesting that MGMT promoter methylation status in elderly patients has a similar distribution and prognostic importance to those seen in younger patients [24,25]. Although testing the MGMT promoter methylation status in younger patients (outside a clinical trial) currently does not influence the decision about which treatment the patient should receive, this might be a helpful adjunct in elderly, more frail patients in whom the risks and benefits of adding TMZ need to be weighed with particular caution.…”

“…Although the reported rates of acute toxicities do not seem much different between younger and older patients, the elderly may have a higher rate of delayed cognitive decline [25]. There are data suggesting that MGMT promoter methylation status in elderly patients has a similar distribution and prognostic importance to those seen in younger patients [24,25].…”

“…Also in this trial, there is no direct comparison with the Stupp regimen, and conclusions will need to be drawn from a historical comparison. Survival appears substantially inferior with single-modality chemotherapy or irradiation to that seen with combination therapy in elderly patients [3, 24,25].…”

Radiosurgery with chemotherapy as an alternative to RT for glioblastoma multiforme patients 65 years old or older: a prospective review of 40 patients

“…The optimal management of this CNS neoplasm in the elderly is still a matter of debate, with several combinations beings studied. A number of small, prospective studies have shown the benefit of a tri-modal approach involving chemotherapy, radiation therapy, and surgical resection in elderly patients [4][5][6][7][8]. Most recently, RTOG studied the use of upfront stereotactic radiosurgery, radiation therapy, and carmustine (BCNU) versus radiation therapy and BCNU alone.…”