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

• Published in: Journal of clinical oncology Vol. 25; no. 27; pp. 4187 - 4193
• Main Authors: MÖBUS, Volker, WANDT, Hannes, FRICKHOFEN, Norbert, BENGALA, Carmelo, CHAMPION, Kim, KIMMIG, Rainer, OSTERMANN, Helmut, HINKE, Axel, LEDERMANN, Jonathan A
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20-09-2007; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Disease-Free Survival; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Melphalan - administration & dosage; Middle Aged; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Paclitaxel - administration & dosage; Stem Cell Transplantation - methods; Time Factors; Treatment Outcome; Tumors; Phase III trial; European group for blood and marrow transplantation; Ovary cancer; Hematopoietic cell; Malignant tumor; Standards; Blood; Female genital diseases; First line treatment; Ovarian diseases; Chemotherapy; Cancerology; Sequential; Clinical trial; Advanced stage; High dose; Comparative study
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2006.09.7527

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.
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%.
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).
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.