Intraperitoneal cisplatin therapy in ovarian cancer: Comparison with standard intravenous carboplatin and paclitaxel

Abstract

Epithelial ovarian cancer remains the leading cause of death from gynecologic cancer in the United States with an estimated 15,300 deaths in 2006 [ [1] Jemal A. Siegel R. Ward E. Murray T. Xu J. Smigal C. et al. Cancer Statistics, 2006. CA Cancer J. Clin. 2006; 56: 106-130 Crossref PubMed Scopus (5485) Google Scholar ]. Cytoreductive surgery, the cornerstone of initial therapy, is followed by chemotherapy for management of residual disease. Two randomized trials [ 2 McGuire W.P. Hoskins W.J. Brady M.F. Kucera P.R. Partridge E.E. Look K.Y. et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N. Engl. J. Med. 1996; 334: 1-6 Crossref PubMed Scopus (2740) Google Scholar , 3 Piccart M.J. Bertelsen K. James K. Cassidy J. Mangioni C. Simonsen E. et al. Randomized intergroup trial of cisplatin–paclitaxel versus cisplatin–cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J. Natl. Cancer Inst. 2000; 92: 699-708 Crossref PubMed Scopus (898) Google Scholar ] established cisplatin plus paclitaxel (24-h infusion) to be the standard of care in the 1990s, and subsequent larger randomized trials [ 4 Ozols R.F. Bundy B.N. Greer B.E. Fowler J.M. Clarke-Pearson D. Burger R.A. et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J. Clin. Oncol. 2003; 21: 3194-3200 Crossref PubMed Scopus (1741) Google Scholar , 5 du Bois A. Lück H.-J. Meier W. Adams H.P. Mobus V. Costa S. et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J. Natl. Cancer Inst. 2003; 95: 1320-1330 Crossref PubMed Google Scholar ] demonstrated that carboplatin with paclitaxel (3-h infusion) was the preferable regimen due to a reduction in toxicity, superior quality of life, increased ease of administration, and no evidence of inferiority compared to cisplatin/paclitaxel. A recent international consensus conference recommended intravenous (IV) carboplatin/paclitaxel as the standard regimen against which new treatments should be compared [ [6] du Bois A. Quinn M. Thigpen T. Vermorken J. Avall-Lundquist E. Bookman M. et al. 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann. Oncol. 2005; 16: viii7-viii12 Crossref PubMed Scopus (402) Google Scholar ]. The intraperitoneal (IP) delivery of chemotherapy, particularly cisplatin, has been posited to improve long-term outcomes for women with advanced ovarian cancer based on results from phase III trials. However, interpretation of these data has generated controversy, primarily due to the increased toxicity associated with IP therapy and to the control arms used in the randomized trials. In the recent phase III trials of IP therapy, the control arm consisted of the outdated regimen of IV cisplatin and 24-h paclitaxel. Based on an exploratory cross-trial analysis, we hypothesize that there is no statistically significant improvement in survival if the IP regimen were compared to the current global standard of IV carboplatin and 3-h paclitaxel. Potential reasons to explain this outcome are addressed, as well as justification for a new randomized trial to prospectively evaluate the hypothesis.