title: Treatment of newly diagnosed glioblastoma multiforme with carmustine, cisplatin and etoposide followed by radiotherapy. A phase II study.
abstract: 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 200 mg/m2 i.v. on day 1, cisplatin 20 mg/m2 i.v. on day 1-5 and etoposide (VP-16) 100 mg/m2 i.v. on day 1-5, given every five weeks and followed by localized radiation, 60 Gy 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.
authors.affiliation: Department of Neuroradiology, National University Hospital, Rigshospitalet, Copenhagen, Denmark. ulassen@rh.dk
authors.forename: U
authors.initials: U
authors.lastname: Lassen
authors.forename: P E
authors.initials: PE
authors.lastname: Kristjansen
authors.forename: A
authors.initials: A
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Kosteljanetz
authors.forename: H S
authors.initials: HS
authors.lastname: Poulsen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D002945:Cisplatin; D002330:Carmustine