title: Kinetic modeling and efficacy of intraperitoneal paclitaxel combined with intravenous cyclophosphamide and carboplatin as first-line treatment in ovarian cancer.
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.
  
  
  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 I/II was reported in only 20% and myalgia in 24% of patients and were fully reversible. After treatment 13 of 18 (72%) of the patients had 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, University Hospital Groningen, Groningen, The Netherlands.
authors.forename: L S
authors.initials: LS
authors.lastname: Hofstra
authors.forename: A M E
authors.initials: AM
authors.lastname: Bos
authors.forename: E G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: A G J
authors.initials: AG
authors.lastname: van der Zee
authors.forename: A T M
authors.initials: AT
authors.lastname: Willemsen
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
authors.forename: J G
authors.initials: JG
authors.lastname: Aalders
authors.forename: P H B
authors.initials: PH
authors.lastname: Willemse
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel