Originally published as JCO Early Release 10.1200/JCO.2006.09.7527 on August 13 2007

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Phase III Trial of High-Dose Sequential Chemotherapy With Peripheral Blood Stem Cell Support Compared With Standard Dose Chemotherapy for First-Line Treatment of Advanced Ovarian Cancer: Intergroup Trial of the AGO-Ovar/AIO and EBMT

Volker Möbus, Hannes Wandt, Norbert Frickhofen, Carmelo Bengala, Kim Champion, Rainer Kimmig, Helmut Ostermann, Axel Hinke, Jonathan A. Ledermann

From the Department of Obstetrics and Gynecology, Städtisches Klinikum Frankfurt a.M.-Höchst; Department of Hematology and Oncology, Klinikum Nürnberg; Department of Hematology and Oncology, Dr Horst Schmidt Kliniken Wiesbaden; Department of Obstetrics and Gynecology, University Hospital Essen, Germany; Department of Hematology and Oncology, University Hospital Grosshadern, München; Wissenschaftlicher Service Pharma (WiSP), Langenfeld, Germany; Department of Hematology and Oncology, University Hospital Modena, Italy; European Group for Blood and Marrow Transplantation, University College Hospital; and the Department of Oncology, University College London, London, United Kingdom

Address reprint requests to Volker Möbus, MD, Department of Obstetrics and Gynecology, Städtisches Klinikum, Gotenstraβe 6-8, D-65929 Frankfurt, Germany; e-mail: vmoebus{at}skfh.de

Purpose Although ovarian cancer is one of the most chemotherapy-sensitive solid tumors, cure after radical surgery and chemotherapy is uncommon. A randomized trial comparing high-dose sequential chemotherapy with peripheral blood stem cell (PBSC) support with platinum-based combination chemotherapy was conducted to investigate whether dose-intensification improves outcome.

Patients and Methods One hundred forty-nine patients with untreated ovarian cancer were randomly assigned after debulking surgery to receive standard combination chemotherapy or sequential high-dose (HD) treatment with two cycles of cyclophosphamide and paclitaxel followed by three cycles of HD carboplatin and paclitaxel with PBSC support. HD melphalan was added to the final cycle. The median age was 50 years (range, 20 to 65 years) and International Federation of Gynecology and Obstetrics stage was IIb/IIc in 4%, III in 78%, and IV in 17%.

Results Seventy-six percent of patients received all five cycles in the HD arm and the main toxicities were neuro-/ototoxicity, gastrointestinal toxicity, and infection and one death from hemorrhagic shock. After a median follow-up of 38 months, the progression-free survival was 20.5 months in the standard arm and 29.6 months in the HD arm (hazard ratio [HR], 0.84; 95% CI, 0.56 to 1.26; P, .40). Median overall survival (OS) was 62.8 months in the standard arm and 54.4 months in the HD arm (HR, 1.17; 95% CI, 0.71 to 1.94; P, .54).

Conclusion This is the first randomized trial comparing sequential HD versus standard dose chemotherapy in first-line treatment of patients with advanced ovarian cancer. We observed no statistically significant difference in progression-free survival or OS and conclude that HD chemotherapy does not appear to be superior to conventional dose chemotherapy.

published online ahead of print at www.jco.org on August 13, 2007.

Supported by unrestricted educational grants from Amgen and Bristol-Myers Squibb.

V.M. and J.A.L. were the co-chairmen of the AGO/AIO and EBMT Intergroup.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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• Ovarian Cancer: Is Dose Intensity Dead?
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  JCO 2007 25: 4157-4158 [Full Text]

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