Phase III Trial of Carmustine and Cisplatin Compared With Carmustine Alone and Standard Radiation Therapy or Accelerated Radiation Therapy in Patients With Glioblastoma Multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials

Journal of Clinical Oncology, Vol 24, No 24 (August 20), 2006: pp. 3871-3879

PURPOSE: In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT).

PATIENTS AND METHODS: After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). RT
Patients received either SRT consisting of 1.80 Gy daily for 36 days (64.8 Gy) or ART with 1.60 Gy twice daily for 15 days (48.0 Gy). RT for patients on arms C and D began 8 weeks after random assignment to coincide with cycle 2 of chemotherapy. The biologic equivalence dose of the ART schedule is 56 Gy10 and 74 Gy3 compared with 77 Gy10 and 104 Gy3 for the SRT regimen.

RESULTS: Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33).

CONCLUSION: Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.