Kinetic modeling and efficacy of intraperitoneal paclitaxel combined with intravenous cyclophosphamide and carboplatin as first-line treatment in ovarian cancer

Objective. The purpose of this study was to determine the efficacy, tolerability, and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous (iv) carboplatin and cyclophosphamide. Patients and methods. Twenty-five newly diagnosed patients with Stage IC-IV epithelial ovarian cancer received ip paclitaxel with iv carboplatin and cyclophosphamide as a first-line treatment. Paclitaxel pharmacokinetics was determined during the first cycle on day 1 or 8. Results. This regimen was well tolerated, as abdominal pain and hematological toxicities were minor, while neurotoxicity grade 1/11 was reported in only 20% and myalgia in 24% of patients and were fully reversible. After treatment 13 of 18 (72%) of the patients a no evidence of disease. At a median follow-up of 30 months patients with residual disease after surgery (n = 10) had a median progression-free survival (PSF) of 13 months; for the optimally debulked group (n = 15) the actuarial PFS was 60% at 48 months. The elimination of paclitaxel from the peritoneal cavity and plasma followed first-order kinetics and was not influenced by adding carboplatin with cyclophosphamide. Conclusion. This regimen was well tolerated, with minimal hematologic or neurotoxicity, and allowed the application of a triple-drug schedule without compromising dose intensity. To judge its efficacy, comparison with a standard iv paclitaxel-based schedule should be performed in a formal phase III study. (C) 2002 Elsevier Science (USA).