Pre-irradiation carboplatin and etoposide and accelerated hyperfractionated radiation therapy in patients with high-grade astrocytomas: a phase II study

Abstract

Purpose: To investigate feasibility, activity and toxicity of pre-irradiation chemotherapy (CHT) in patients with newly diagnosed high-grade astrocytoma.Material and Methods: Thirty-five patients with glioblastoma multiform (GBM) and ten patients with anaplastic astrocytoma (AA) entered into this study. Three weeks after surgery patients started their CHT consisting of two cycles of carboplatin (CBDCA) (C) 400 mg/m2, day 1 and etoposide (VP 16) (E) 120 mg/m2, days 1–3, given in a 3-week interval. One week after the second cycle of CE, accelerated hyperfractionated radiation therapy (ACC HFX RT) was introduced with tumor dose of 60 Gy in 40 fractions in 20 treatment days in 4 weeks, 1.5 Gy b.i.d. fractionation.Results: Responses to two cycles of CE could be evaluated in 29 (67%) of 43 patients who received it. Fourteen patients were found impossible to determine radiographic response due to an absence of post-operative contrast enhancement because they were all grossly totally resected. There were 7, 24% (95% confidence intervals - CI, 9–40%), PR (2 AA and 5 GBM), 19 SD, and 3 PD. After RT, of those 29 patients, there were 3 CR and 11 PR (overall objective response rate was 48% (95% CI, 30–67%)), 12 SD, and 3 PD. Median survival time (MST) for all 45 patients is 14 months (95% CI, 11–20 months, while median time to progression (MTP) for all patients is 12 months (95% CI, 8–16 months). Toxicities of this combined modality approach were mild to moderate, with the incidences of CHT-induced grade 3 leukopenia, being 5% (95% CI, 0–11%), and grade 3 thrombocytopenia being 7% (95% CI, 0–15%). Of RT-induced toxicity, grade 1 external otitis was observed in 26% (95% CI, 13–39%), while nausea, vomiting and somnolence were each observed in 5% (95% CI, 0–11%) patients.Conclusion: Pre-irradiation CE and ACC HFX RT was a feasible treatment regimen with mild to moderate toxicity, but failed to improve results over what usually would be obtained with ‘standard’ approach in this patient population.