Treatment of Newly Diagnosed Glioblastoma Multiforme with Carmustine,Cisplatin and Etoposide Followed by Radiotherapy. A Phase II Study

A meta-analysis and several studies of patients with grade III and IV gliomas have indicated that the addition of nitrosurea based chemotherapy to surgery and radiation may improve survival. We performed a phase II study of pre-irradiative chemotherapy with BCNU, cisplatin and etoposide. This implies a short total treatment duration and a reliable response evaluation.The treatment schedule was three cycles of BCNU 200mg/m² i.v. on day 1, cisplatin 20mg/m² i.v. on day 1–5 and etoposide (VP-16) 100mg/m² i.v. on day 1–5, given every five weeks and followed by localized radiation, 60Gy in 30 fractions. Twenty-nine patients with newly diagnosed glioblastoma multiforme (GBM), mean age 50 (27–66) and performance status (PS) 0–2 were included.Using the Macdonald criteria 33% had partial remission (PR), 41% stable disease (SD) and 26% progressive disease (PD) after chemotherapy. After additional radiation 44% had PR, 37% SD and 19% PD. Non-hematological toxicity and leukopenia was mild, but thrombocytopenia (TP) frequent. Grade III and IV TP occurred in 25% and 57% respectively, and grade III bleeding in 45%. No severe or fatal complications was seen. Median time to progression (TTP) was 7.6 months (6.0–9.1) and median survival was 11.4 months (10.1–12.7).We conclude that this regimen is effective and feasible in patients with GBM. The short course pre-irradiatory chemotherapy may be less cumbersome than adjuvant chemotherapy and the regimen may be even more active in grade III gliomas.