1. ¹Department of Oncology, Norwegian Radium Hospital and University of Oslo, Oslo, Norway
2. ²Department of Urology, Maria Sklodowska – Curie Memorial Cancer Center, Warsaw, Poland
3. ³Department of Academic Radiotherapy, Royal Marsden Hospital, Sutton, UK
4. ⁴Department of Oncology, Klinikum Nürnberg, Nürnberg, Germany
5. ⁵Department of Internal Medicine, Sint Radboud University Hospital, Nijmegen, The Netherlands
6. ⁶Department of Urology, Medical Radiological Research Center, Obninsk (formerly: Cancer Research Center, Moskow, Russia), Russia
7. ⁷Department of Oncology, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium
8. ⁸Data Center, Data Management Unit, EORTC Data Center, Brussels, Belgium
9. ⁹Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence: Professor SD Fosså, Rikshospitalet – Radiumhospitalet Trust, Department of Clinical Cancer Research, Montebello, NO 0310 Oslo 3, Norway. E-mail: s.d.fossa@klinmed.uio.no

Received 8 August 2005; Revised 14 August 2005; Accepted 19 September 2005; Published online 25 October 2005.

Abstract

New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9–79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7–66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5–91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6–93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.