Phase I study of weekly nab-paclitaxel combined with S-1 in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer

Cancer Sci. 2015 Jun;106(6):734-739. doi: 10.1111/cas.12658. Epub 2015 Apr 9.

Abstract

We conducted a phase I study of a weekly nab-paclitaxel and S-1 combination therapy in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer. The primary objective was to estimate the maximum tolerated and recommended doses. Each treatment was repeated every 21 days. Levels 1, 2a, 2b, and 3 were set depending on the S-1 dose (65 or 80 mg/m(2) ) and nab-paclitaxel infusion schedule (days 1 and 8 or days 1, 8, and 15). Fifteen patients were enrolled. Dose-limiting toxicity was observed in one patient at Level 3 (100 mg/m(2) nab-paclitaxel on days 1, 8, and 15 with 80 mg/m(2) S-1 daily for 14 days, followed by 7 days of rest). Although the maximum tolerated dose was not reached, the recommended dose was determined to be Level 3. Neutropenia was the most frequent grade 3-4 treatment-related adverse event. For patients with measurable lesions, the response rate was 50.0% and the median time to treatment failure and median progression-free survival was 13.2 and 21.0 months, respectively. The present results show the feasibility and potential for long-term administration of this combination therapy.

Keywords: Combination chemotherapy; S-1; metastatic breast cancer; nab-paclitaxel; phase I study.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Albumins / adverse effects
  • Albumins / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Oxonic Acid / pharmacokinetics
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics
  • Receptor, ErbB-2 / analysis*
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Tegafur / pharmacokinetics

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel