Methotrexate, TMZ, and Rituximab Followed by hWBRT Safe for Patients With CNS Lymphoma
Treatment of primary central nervous system lymphoma with methotrexate, TMZ, and rituximab, followed by hWBRT and subsequent TMZ was safe.
Treatment of primary central nervous system lymphoma with methotrexate, temozolomide (TMZ), and rituximab, followed by hyperfractionated whole-brain radiotherapy (hWBRT) and subsequent TMZ was safe, with the best 2-year overall survival rate and progression-free survival achieved in any Radiation Therapy Oncology Group primary CNS lymphoma trial, according to studies published in the Journal of Clinical Oncology.1
The phase 1 study was performed to determine the maximum tolerated dose of TMZ. The phase 2 trial's endpoint was the 2-year overall survival rate. Secondary endpoints included preirradiation response rates, progression-free survival, neurologic toxicities, and quality of life.
For the phase 1 study, 12 patients received increased TMZ doses from 100 to 150 to 200 mg/m2. Patients were treated with rituximab 375 mg/m2 3 days prior to cycle 1; methotrexate 3.5 mg/m2 with leucovorin on weeks 1, 3, 5, 7, and 9; TMZ daily for 5 days on weeks 4 and 8; hWBRT 1.2 Gy twice daily on weeks 11 to 13 (38 Gy); and TMZ 200 mg/m2. A total of 53 patients were treated in the phase 2 trial.
Results from the phase 1 trial showed that the maximum tolerated dose was 100 mg/m2 for TMZ and dose-limiting toxicities were hepatic and renal.
In the phase 2 trial, 2-year overall survival was 80.8% and progression-free survival was 63.6% at a median follow-up of 3.6 years. Objective response rate was 85.7%. A total of 66 patients had grade 3 and 4 toxicities prior to hWBRT and 45% had grade 3 and 4 toxicities related to post-hWBRT. Quality of life and cognitive function improved or stabilized post HWBRT.
- Glass J, Won M, Schultz CJ, et al. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG oncology RTOG 0227 [published online ahead of print March 28, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.64.8634.