Currently Enrolling Trials
Temodar (temozolomide) is an alkylating drug.
Temodar is specifically indicated for the treatment of adult patients with:
- Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment.
- Refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine
Temodar is supplied as capsules for oral use or as an intravenous injection. The recommended dosing is:
Newly Diagnosed Glioblastoma:
- 75 mg/m2 once daily for 42 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m2 once daily for Days 1 to 5 of each 28-day cycle for 6 cycles. May increase maintenance dose to 200 mg/m 2 for cycles 2 to 6 based on toxicity.
- Provide Pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less.
Refractory Anaplastic Astrocytoma:
- Initial dose of 150 mg/m2 once daily on Days 1 to 5 of each 28-day cycle.
Mechanism of Action
Temodar (temozolomide) is an alkylating drug. Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3- methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA. Alkylation (methylation) occurs mainly at the O6 and N7 positions of guanine.
Adverse effects associated with the use of Temodar may include, but are not limited to, the following:
The most common Grade 3 to 4 hematologic laboratory abnormalities (≥10% incidence) in patients with anaplastic astrocytoma are: decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.
Clinical Trial Results
Newly diagnosed glioblastoma
The efficacy of Temodar was evaluated in Study MK-7365-051, a randomized (1:1), multicenter, open-label trial. Eligible patients were required to have newly diagnosed glioblastoma. Patients were randomized to receive either radiation therapy alone or concomitant Temodar 75 mg/m2 once daily starting the first day of radiation therapy and continuing until the last day of radiation therapy for 42 days (with a maximum of 49 days), followed by Temodar 150 mg/m2 or 200 mg/m 2 once daily on Days 1 to 5 of each 28-day cycle, starting 4 weeks after the end of radiation therapy and continuing for 6 cycles. In both arms, focal radiation therapy was delivered as 60 Gy/30 fractions and included radiation to the tumor bed or resection site with a 2- to 3-cm margin. PCP prophylaxis was required during the concomitant phase regardless of lymphocyte count and continued until recovery of lymphocyte count to Grade 1 or less. The major efficacy outcome measure was overall survival. A total of 573 patients were randomized. At the time of disease progression, Temodar was administered as salvage therapy in 161 patients of the 282 (57%) in the radiation therapy alone arm and 62 patients of the 277 (22%) in the Temodar and radiation therapy arm. The addition of concomitant and maintenance Temodar to radiation therapy for the treatment of patients with newly diagnosed glioblastoma showed a statistically significant improvement in overall survival compared to radiotherapy alone. The median survival was increased by 2.5 months in the Temodar arm.
Refractory Anaplastic Astrocytoma
The efficacy of Temodar was evaluated in Study MK-7365-006, a single-arm, multicenter trial. Eligible patients had anaplastic astrocytoma at first relapse and a baseline Karnofsky performance status (KPS) of 70 or greater. Patients had previously received radiation therapy and may also have previously received a nitrosourea with or without other chemotherapy. Fifty-four patients had disease progression on prior therapy with both a nitrosourea and procarbazine and their malignancy was considered refractory to chemotherapy (refractory anaplastic astrocytoma population). Temodar capsules were given on Days 1 to 5 of each 28-day cycle at a starting dose of 150 mg/m2 /day. If ANC was ≥1.5 x 109 /L and platelet count was ≥100 x 109 /L at the nadir and on Day 1 of the next cycle, the Temodar dose was increased to 200 mg/m2 /day. The major efficacy outcome measure was progression-free survival at 6 months and the additional efficacy outcome measures were overall survival and overall response rate.
In the refractory anaplastic astrocytoma population, the overall response rate (CR+PR) was 22% (12 of 54 patients) and the complete response rate was 9% (5 of 54 patients). The median duration of all responses was 50 weeks (range: 16 to 114 weeks) and the median duration of complete responses was 64 weeks (range: 52 to 114 weeks). In this population, progression-free survival at 6 months was 45% and progression-free survival at 12 months was 29%. Median progression-free survival was 4.4 months. Overall survival at 6 months was 74% and 12-month overall survival was 65%. Median overall survival was 15.9 months.