Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer: A phase I and feasibility trial of the Gynecologic Oncology Group

Mark A. Morgan*, Kathleen M. Darcy, Peter G. Rose, Koen DeGeest, Michael A. Bookman, James K. Aikins, Michael W. Sill, Robert S. Mannel, Cecilia Allievi, Merrill J. Egorin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Purpose: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. Methods: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m2. Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over ≥ 4cycles. Results: PPX at 225 mg/m2 resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m2 and then to 135 mg/m2. PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. Conclusions: The recommended dose of PPX of 135 mg/m2 with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalGynecologic Oncology
Volume110
Issue number3
DOIs
StatePublished - Sep 2008
Externally publishedYes

Keywords

  • Carboplatin
  • Chemotherapy
  • Ovarian cancer
  • Paclitaxel poliglumex
  • Phase I trial

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