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A phase I study evaluating the safety and pharmacokinetics of weekly paclitaxel and carboplatin in relapsed ovarian cancer
  1. A. L. Leiser*,
  2. F. C. Maluf*,
  3. D. S. Chi,
  4. P. Sabbatini*,
  5. M. L. Hensley*,
  6. L. Schwartz,
  7. E. Venkatraman§,
  8. D. Spriggs* and
  9. C. Aghajanian*
  1. * Division of Solid Tumor Oncology, Department of Medicine, Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York
  2. Department of Surgery, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, New York
  3. Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York
  4. § Division of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
  1. Address correspondence and reprint requests to: Carol Aghajanian, MD, Division of Solid Tumor Oncology, Department of Medicine, Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Email: aghajanc{at}mskcc.org

Abstract

This phase I study sought to determine the toxicity profile, pharmacokinetics, and antitumor activity of giving carboplatin every 3 weeks and paclitaxel weekly in patients with relapsed ovarian cancer. Eligible patients with relapsed epithelial ovarian cancer and prior treatment with platinum- and paclitaxel-based therapy were treated with an escalating regimen of carboplatin (day 1) at an area under the curve (AUC) of 4–6 and 1-h infusions of paclitaxel (days 1, 8, and 15) at 50–80 mg/m2 cycled at 3-week intervals. Pharmacokinetic studies were performed on the first day of cycles 1 and 2. All patients had a platinum-free interval of greater than 6 months from the most recent platinum treatment. A total of 77 cycles were administered to 16 patients, with a similar median number of cycles per patient at each dose level varying from 4.6 to 5.3. Febrile neutropenia and grade 4 thrombocytopenia were the dose-limiting toxicities at dose levels 3 and 4 after the third cycle, with no mucositis, nausea, vomiting, or peripheral neuropathy observed greater than grade 2. The maximum tolerated dose of carboplatin was an AUC of 5 and 80 mg/m2 for paclitaxel. Pharmacokinetic analysis showed a marginal statistical difference with regard to reduced systemic paclitaxel concentration after cycle 2 compared with cycle 1 (P= 0.06). Of nine patients evaluable for a radiographic response, the response rate was 66.6% with a complete response of 33.3%. All five patients with nonmeasurable disease achieved a biochemical response. The combination of carboplatin given every 3 weeks at an AUC of 5 and 1-h weekly paclitaxel at 80 mg/m2 is a feasible and reasonably well-tolerated regimen and may have significant antitumor activity in relapsed ovarian cancer patients.

  • carboplatin
  • ovarian cancer
  • paclitaxel
  • relapsed
  • weekly

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