Cytoreductive surgery has played an important role in the management of advanced ovarian cancer since Griffiths demonstrated in 1975 that an inverse relationship existed between overall survival and residual tumor size.3 This has been confirmed in subsequent studies, and a meta-analysis of 81 cohorts of patients with stage III or IV disease from clinical trials conducted between 1989 and 1998 suggested that for every 10% increase in the proportion of patients achieving maximal cytoreduction—defined in this meta-analysis as residual disease ?3cm in maximal dimension—there was an approximate 5.5% improvement in length of overall survival.4 The definition of optimal debulking has been discussed in the literature. A 2001 survey of gynecological oncologists revealed that 12% defined optimal reduction as no residual disease, 13.7% used a 5mm minimum threshold, 60.8% used a 1cm threshold, and 12.6% used a 1.5–2cm threshold.5 Currently, a widely accepted Gynecologic Oncology Group (GOG) definition states that optimal cytoreduction surgery leaves less than 1cm in maximum residual cancer.6
The concept of intra-peritoneal (IP) chemotherapy for ovarian cancer involves the regional delivery of cytotoxic drugs directly into the peritoneal cavity, resulting in higher concentrations than can be safely reached with systemic intravenous chemotherapy alone, a hypothesis that has been confirmed in pharmacokinetic studies.7 Three US-based phase III clinical trials have now evaluated the efficacy of IP therapy in optimally cytoreduced advanced ovarian cancer. The first of these trials enrolled 654 patients with stage III disease and who were optimally cytoreduced to residual cancer of ?2 centimeters.8 Patients were randomized to either intravenous (IV) cyclophosphamide 600mg/m2 and IV cisplatin 100mg/m2 or intravenoous (IV) cyclophosphamide 600mg/m2 and IP cisplatin 100mg/m2. In this trial, the median survival of the IP group was 49 months and that of the IV group 41 months, with a hazard ratio for death of 0.72 in the IP group (p=0.02). However, the benefit of IP cisplatin was questioned because paclitaxel was not given as part of either regimen.