Annals of Oncology 16 (Supplement 8) viii13–viii19, 2005 doi:10.1093/annonc/mdi962 Clinical trials in ovarian carcinoma: requirements for standard approaches and regimens T. Thigpen 1 *, G. Stuart 2 , A. du Bois 3 , M. Friedlander 4 , K. Fujiwara 5 , J. P. Guastalla 6 , S. Kaye 7 , H. Kitchener 8 , G. Kristensen 9 , R. Mannel 1 , W. Meier 3 , B. Miller 10 , A. Poveda 11 , D. Provencher 2 , F. Stehman 1 & I. Vergote 12 Gynecologic Cancer Intergroup (GCIG) and its member organizations: 1 GOG (USA); 2 NCIC-CTG (Canada); 3 AGO-OVAR (Germany); 4 ANZGOG (Australia–New Zealand); 5 JGOG (Japan); 6 GINECO (France); 7 SGCTG (Scotland, UK); 8 MRC/NCRI (UK); 9 NSGO (Scandinavia); 10 RTOG (USA); 11 GEICO (Spain); 12 EORTC (Europe) The 3rd International Ovarian Cancer Consensus Conference (OCCC), held 3–5 September 2004, in Baden-Baden, Germany, addressed 12 questions critical to the future directions of clinical research into the treatment of newly diagnosed ovarian cancer. Four of these questions examined issues related to the current standard of care and to what should, for now, constitute a proper control arm in future phase III clinical trials. These questions are listed in Table 1. Consensus on the answer to these four questions is crucial to the interpretation of major clinical trials. Such a consensus will encourage the use of similar standards in each major trial and thus will provide a common basis for interpretation. This article will provide a detailed discussion of the rationale for the un- animous consensus achieved for each of these four questions. Surgery in trials of newly diagnosed patients The first question asks simply whether there is a need to define strictly the extent and type of surgery for patients in first-line trials. Divergent approaches to surgical requirements in recently reported major trials prompted this question. For example, in the major trials examining the inclusion of a taxane in front-line trials, quite different approaches to surgical requirements are apparent. The two Gynecologic Oncology Group trials (GOG protocols 111 [1] and 132 [2]) conducted in the USA employed strict definitions for the extent and type of surgery and required accurate surgical staging as well as an aggressive attempt at surgical bulk reduction. At the other extreme, the Medical Research Council (MRC) trial, ICON3 [3], did not mandate formal FIGO surgical staging. Although stage was reported, one cannot assume accurate surgical staging in the absence of a for- mal requirement. The remaining trial, the European–Canadian OV-10 study [4], had requirements closer to the GOG approach than to the MRC approach. That such divergent surgical approaches can result in very different outcomes is best illustrated by the apparently contradic- tory results of two large trials of interval surgical cytoreduction [5, 6]. The first of these two trials conducted by the EORTC in Europe randomized patients with advanced ovarian carcinoma who had been deemed not amenable to surgical cytoreduction by the initial surgeon to either six cycles of cyclophosphamide plus cisplatin or to three cycles of the same chemotherapy followed by an interval attempt at surgical cytoreduction followed by three more cycles of the same chemotherapy [5]. The results suggested a progression-free and overall survival advantage for those patients assigned to interval surgical cytoreduction. The second study conducted by the GOG in the USA random- ized a similar group of patients to either six cycles of paclitaxel plus cisplatin or three cycles of paclitaxel/cisplatin followed by interval surgical cytoreduction followed by three more cycles of paclitaxel/cisplatin [6]. In contrast to the EORTC trial, the GOG trial showed no advantage for those patients assigned to the interval debulking. The key to the proper interpretation of these two trials lies in the aggressiveness of the initial attempt at surgical cytoreduction prior to study entry. In the EORTC study, patients were seen by a variety of surgeons, most of whom had not received formal training in surgical bulk reduction and only interval debulking was centralized. Patients entering the GOG trial were, for the most part, seen by trained gynecologic oncol- ogists. Each underwent a very aggressive attempt at surgical bulk reduction if at all possible. The nature of the initial surgery thus determined whether interval surgical bulk reduction re- sulted in patient benefit, and the two trials actually do not con- tradict each other. The data from these two studies argue for the necessity of strict surgical entry criteria as a part of randomized trials of ovarian carcinoma since differences in the initial sur- gery can impact outcomes and alter conclusions from the trial. These considerations led to the unanimous answer that there is a need to define strictly the extent and type of surgery for patients in front-line trials. The basis for this conclusion was three-fold. First, clinical trials investigating the management of celomic epithelial carcinoma of the ovary and peritoneal cav- ity, the target population of essentially all major trials of ‘ovarian cancer’, should ensure that only patients with this diagnosis, not those with gastrointestinal malignancies or ovarian tumors of low malignant potential, are included [7–9]. Secondly, results of therapy in any given trial depend to a great degree on the composition of the study population with regard to stage or *Correspondence to: Dr T. Thigpen, Department of Medicine, Division of Oncology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MI 39216, USA. 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