Concurrent accelerated hyperfractionated radiation therapy and carboplatin/etoposide in patients with malignant glioma: long-term results of a phase II study

Purpose: Feasibility, antitumor activity and toxicity of accelerated hyperf ractionated radiation therapy (Acc Hfx RT) and concurrent carboplatin/etopo side (CBDCA/VP 16) chemotherapy were investigated in patients with malignan t glioma. Material and methods: Seventy-nine patients with either glioblastoma multif orme (GBM) (n = 61) or anaplastic astrocytome (AA) (n = 18) entered into a phase II study on the use of Acc Hfx RT with 60 Gy in 40 fractions in 20 tr eatment days over 4 weeks and concurrent CBDCA, 200 mg/m(2), and VP 16, 200 mg/m(2), both given once weekly during the RT course. Results: The median survival time for all 79 patients was 14 months (11 and 44 months for GBM and AA patients, respectively), while the 2- and 4-year survival was respectively 33% and 11% for all patients, 13% and 1.6% for GB M patients, and 100% and 44% for AA patients (p < 0.0001). The median time to progression for all patients was 12 months (9 and 40 months for GBM and AA, respectively), while the 2- and 4-year progression-free survival (PFS) was respectively 28% and 10% (all patients), 10% and 1.7% (GBM) and 89% and 39% (AA) (p < 0.0001). Multivariate analysis showed that age, performance status, and preoperative size of tumor influenced survival in GBM. Only 5 ( 6%) patients experienced grade 3 leukopenia and 6 (8%) patients experienced grade 3 thrombocytopenia. No late PT-induced toxicity was observed to date . Conclusions: Although Acc Hfx RT/CBDCA + VP 16 was feasible and little toxi c, it failed to improve survival/progression-free survival over that obtain ed with other currently used regimens. These results do not justify the inv estigation of this regimen in a phase III trial.