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.