Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients

Cancer Chemother Pharmacol. 2012 Apr;69(4):957-64. doi: 10.1007/s00280-011-1786-6. Epub 2011 Nov 26.

Abstract

Purpose: There is no standard regimen for gemcitabine (Gem)-refractory pancreatic cancer (PC) patients. In a previous phase II trial, S-1 was found to exhibit marginal efficacy. Gem administration by fixed dose rate infusion of 10 mg/m(2)/min (FDR-Gem) should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy. We conducted the phase I/II of FDR-Gem and S-1 (FGS) in patients with Gem-refractory PC.

Methods: The patients received FDR-Gem on day 1 and S-1 orally twice daily on days 1-7. Cycles were repeated every 14 days. Patients were scheduled to receive Gem (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels in the phase I: 800/80 (level 1), 1,000/80 (level 2), 1,200/80 (level 3) and 1,200/100 (level 4). Forty patients were enrolled in the phase II study at recommended dose.

Results: The recommended dose was the level 3. In the phase II, a partial response has been confirmed in seven patients (18%). The median overall survival time and median progression-free survival time are 7.0 and 2.8 months, respectively. The common adverse reactions were anorexia, leukocytopenia and neutropenia.

Conclusion: This combination regimen of FGS is active and well tolerated in patients with Gem-refractory PC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Resistance, Neoplasm
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Pancreatic Neoplasms / drug therapy*
  • Tegafur / administration & dosage
  • Tegafur / adverse effects

Substances

  • Drug Combinations
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Gemcitabine