State-of-the-art treatment of high-grade brain tumors

The incidence of primary brain tumors has rapidly increased in recent years. The current standard of care for patients with high-grade malignant glioma is resection followed by radiotherapy. However, the use of adjuvant chemotherapy and the standard of care at first relapse are still under debate for patients with glioblastoma multiforme and anaplastic astrocytoma. Meta-analyses have suggested that adjuvant chemotherapy, specifically with nitrosourea-based regimens, is associated with improved survival. However, no randomized, controlled trial has shown a clear advantage for adjuvant chemotherapy in these patients. Cumulative toxicity associated with both radiotherapy and chemotherapy, as well as resistance to nitrosourea-based regimens related to exposure in the adjuvant setting, prevent the use of radiotherapy and nitrosourea-based regimens at first relapse. The combination of procarbazine, carmustine, and vincristine (PCV) has shown activity at first relapse in patients who have not received adjuvant chemotherapy. Temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ) has shown activity at both first and second relapse in patients who have received prior nitrosourea-based regimens. The better safety profile of temozolomide suggests that it may be preferred to PCV for treatment of patients with recurrent high-grade malignant glioma. Additional randomized, controlled trials are needed to fully define the best option for first-line chemotherapy in both the adjuvant and recurrent settings in patients with high-grade malignant glioma.