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

LS Hofstra*, AME Bos, EGE de Vries, AGJ van der Zee, ATM Willemsen, H Rosing, JH Beijnen, NH Mulder, JG Aalders, PHB Willemse

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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).

Original languageEnglish
Pages (from-to)517-523
Number of pages7
JournalGynecologic Oncology
Volume85
Issue number3
DOIs
Publication statusPublished - Jun-2002

Keywords

  • carboplatin
  • cyclophosphamide
  • intraperitoneal
  • ovarian cancer
  • paclitaxel
  • kinetic modeling
  • GYNECOLOGIC-ONCOLOGY-GROUP
  • RANDOMIZED TRIAL
  • STAGE-III
  • PHASE-III
  • CISPLATIN
  • CHEMOTHERAPY
  • CARCINOMA
  • THERAPY
  • TAXOL
  • PHARMACOKINETICS

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