Temozolomide is used concomitantly with radiation therapy for the treatment of newly diagnosed glioblastoma multiforme in adults; temozolomide also is used as maintenance therapy for glioblastoma multiforme.
The current indication is based on a randomized trial involving 573 patients with newly diagnosed glioblastoma multiforme. Treatment consisted of temozolomide 75 mg/m once daily with radiation therapy for 42 days (up to a maximum of 49 days) followed by a 4-week rest period and then maintenance therapy with up to 6 cycles of temozolomide (150 or 200 mg/m) on days 1-5 of every 28-day cycle; or radiation therapy alone. Salvage therapy with temozolomide was administered upon disease progression to 22% of patients receiving initial therapy with temozolomide and radiation therapy and 57% of patients receiving initial therapy with radiation therapy alone.
Overall survival was prolonged (unadjusted hazard ratio for death: 0.63) and median survival was increased by 2.5 months (14.6 versus 12.1 months) in patients receiving concomitant temozolomide and radiation therapy followed by maintenance therapy with temozolomide compared with those receiving radiation therapy alone as initial therapy for glioblastoma multiforme. Nausea (36 versus 16%), vomiting (20 versus 6%), anorexia (19 versus 9%), constipation (18 versus 6%), and thrombocytopenia (4 versus 1%) occurred more frequently in patients receiving concomitant temozolomide and radiation therapy than in those receiving radiation therapy alone.
Temozolomide is used in the treatment of refractory anaplastic astrocytoma in adults whose disease has progressed after initial therapy with a nitrosourea and procarbazine. The current indication is based on tumor response rates in this population from an uncontrolled phase 2 study. In a single-arm, multicenter study in 162 patients with relapsed anaplastic astrocytoma who had a baseline Karnofsky performance status of 70 or greater, efficacy in a subgroup of 54 patients with refractory disease (i.e., progression following treatment with a nitrosourea and procarbazine) was demonstrated by an overall (complete plus partial) tumor response rate of 22% and a complete response rate of 9%. Median durations of all responses and complete responses were 50 and 64 weeks, respectively. Progression-free survival at 6 and 12 months was 45 and 29%, respectively; median progression-free survival was 4.4 months; 12-month overall survival was 65%; and median overall survival was 15.9 months.