1. ¹Department of Hematology/Oncology, Universitätsklinikum Ulm, Ulm, Germany
2. ²Department of Hematology/Oncology, Charité, Universitätsmedizin Berlin, Klinikum Benjamin-Franklin, Berlin, Germany
3. ³Department of Gynecology, Charité, Universitätsmedizin Berlin, Klinikum Benjamin-Franklin, Berlin, Germany
4. ⁴Department of Hematology/Oncology, Universitätsklinikum Heidelberg, Heidelberg, Germany
5. ⁵Department of Gynecology, Universitätsklinikum Heidelberg, Heidelberg, Germany
6. ⁶Department of Hematology/Oncology, Technische Universität München, Klinikum rechts der Isar, München, Germany
7. ⁷Department of Gynecology, Technische Universität München, Klinikum rechts der Isar, München, Germany
8. ⁸Department of Hematology/Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
9. ⁹Department of Gynecology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
10. ¹⁰Department of Gynecology, Universitätsklinikum Ulm, Ulm, Germany
11. ¹¹Wissenschaftlicher Service Pharma, Langenfeld, Germany

Correspondence: Professor Dr N Frickhofen, Department of Medicine III (Hematology/Oncology), HSK, Dr Horst Schmidt Klinik, D-65199 Wiesbaden, Germany. E-mail: norbert.frickhofen@hsk-wiesbaden.de

Received 27 March 2006; Revised 10 July 2006; Accepted 11 July 2006; Published online 21 August 2006.

Abstract

Ovarian cancer is chemosensitive, but most patients with advanced disease die from tumor progression. As 25% of the patients can be cured by chemotherapy, it is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients with untreated ovarian cancer were entered in a multicenter phase I/II trial of multicycle HDCT. Median age was 46 (19–59 years); International Federation of Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual disease >1 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m²) and paclitaxel (250 mg/m²) were used to collect peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area under curve (AUC) 18–22) and paclitaxel followed by one course of carboplatin and melphalan (140 mg/m²) with or without etoposide (1600 mg/m²). Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient died from treatment-related pneumonitis. At 8 years median follow-up, median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0 months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a multicenter setting. A European phase III trial based on this regimen is evaluating the efficacy of HDCT.