Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): Implications for studies testing initial treatment of brain tumors

Purpose To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. Methods and materials Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of ≥60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m ² of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m² of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m² of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. Results A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. Conclusion The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.