Phase I study of paclitaxel and uracil plus tegafur combination in patients with pretreated metastatic breast cancer: Drug sequencing based on preclinical modelling studies

A. Passardi, R. Maltoni, C. Milandri, L. Cecconetto, I. Massa, W. Zoli, A. Tesei, F. Fabbri, O. Nanni, D. Amadori

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Taxanes and fluoropyrimidines are active in metastatic breast cancer (MBC), and their combination has proven effective in anthracycline- refractory patients. We conducted a phase I study to determine the maximum tolerated dose (MTD) of uracil plus tegafur (UFT) given in combination with leucovorin (LV) and paclitaxel (Pacl) in patients with refractory MBC. Methods: Pacl was infused at a fixed dose of 150 mg/m2 on day 1. UFT, at doses escalated by 50 mg/m2 starting from 200 mg/m2·day, and LV, at a fixed dose of 90 mg/day, were given orally every 8 h for 11 days (days 3-13). Cohorts of at least 3 patients were treated at each dose level, and if 1 experienced dose-limiting toxicity (DLT), a maximum of 3 additional patients were added at the same dose level. MTD was reached if 2 out of the 6 patients experienced DLT. Results: Sixteen patients were enrolled in the study. The most important toxicity observed was hematological. Nonhematological toxicities were paresthesia and myalgia, asthenia, nausea, and mucositis. DLT occurred in only 1 patient (grade 3 hepatic toxicity). Conclusions: The recommended dose for a subsequent phase II trial is Pacl 150 mg/m2 on day 1, and UFT 300 mg/m2 and LV 90 mg on days 3-13, every 2 weeks.

Original languageEnglish
Pages (from-to)118-124
Number of pages7
JournalOncology
Volume72
Issue number1-2
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Leucovorin
  • Metastatic breast cancer
  • Paclitaxel
  • Phase I study
  • Tegafur
  • Translational research
  • Uracil

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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