Phase i study of paclitaxel poliglumex administered weekly for patients with advanced solid malignancies

Monica Mita, Alain Mita, John Sarantopoulos, Chris H. Takimoto, Eric K. Rowinsky, Ofelia Romero, Patrizia Angiuli, Cecilia Allievi, Amy Eisenfeld, Claire F. Verschraegen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background: Paclitaxel poliglumex (PPX, also called Xyotax® or CT-2103) is a water soluble macromolecular drug conjugate that links paclitaxel with a biodegradable polymer, poly-l-glutamic acid. The recommended phase II dose of PPX every 3 week is 235 mg/m2 administered over a 10-min infusion without premedication. This study was designed to determine the MTD and pharmacology of PPX administered weekly to patients with solid malignancies. Methods: The starting dose of weekly PPX was 20 mg/m2. Each cycle consists of 6 weekly treatments with pharmacokinetics of PPX (the conjugated paclitaxel) and unconjugated paclitaxel obtained after the first and sixth dose. Three to six patients were enrolled at each dose level. Toxicity and response were assessed by the NCI Common Toxicity criteria version 2 and RECIST criteria, respectively. Results: Twenty-six patients were treated with PPX at the following dose levels: 20 mg/m2 (five patients), 40 mg/m 2 (four patients), 60 mg/m2 (four patients), 70 mg/m 2 (eight patients) and 80 mg/m2 (five patients). Dose-limiting toxicities, consisting of grade 3 neutropenia, occurred in the 80 mg/m2 cohort during cycle 1. Therefore, the dose recommended for phase II studies was 70 mg/m2. In this cohort, a single dose-limiting event, consisting of diarrhea, was seen. Neuropathy and fatigue were the most common toxicities. No objective responses were noted. Pharmacokinetics was dose-proportional, and the degree of neutropenia related to drug exposure, but not to peak plasma concentration. There was no significant accumulation of conjugated or unconjugated paclitaxel with this dosing schedule. Conclusions: The recommended dose of PPX for subsequent disease-directed studies is 70 mg/m2 weekly.

Original languageEnglish (US)
Pages (from-to)287-295
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume64
Issue number2
DOIs
StatePublished - Jul 1 2009

Keywords

  • Clinical trials
  • PPX
  • Paclitaxel
  • Paclitaxel poliglumex
  • Pharmacodynamics
  • Pharmacokinetics
  • Phase I
  • Solid tumors

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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