Phase II study of S-1 plus leucovorin in patients with metastatic colorectal cancer

Ann Oncol. 2010 Apr;21(4):766-771. doi: 10.1093/annonc/mdp371. Epub 2009 Oct 14.

Abstract

Background: S-1, a novel oral fluoropyrimidine, is well tolerated in patients with metastatic colorectal cancer (mCRC). The response rate of S-1 for colorectal cancer is high, ranging from 35% to 40%. This study aimed to evaluate the safety and efficacy of S-1 combined with oral leucovorin (LV) to enhance antitumor activity in chemotherapy-naive patients with mCRC.

Patients and methods: S-1 was given orally twice daily for two consecutive weeks at a daily dose of 80-120 mg, followed by a 2-week rest period, within a 4-week cycle. LV was given orally twice a day at a daily dose of 50 mg, simultaneously with S-1.

Results: Of the 56 patients with previously untreated mCRC, 32 (57%) had partial responses. The median follow-up period was 27.2 months. The median time to progression was 6.7 months (95% confidence interval 5.4-7.9). The median survival time was 24.3 months. There was no treatment-related death or grade 4 toxicity. The most common grade 3 toxic effects were diarrhea (32%), anorexia (21%), stomatitis (20%), and neutropenia (14%).

Conclusion: S-1 combined with LV therapy demonstrated promising efficacy and acceptable safety in chemotherapy-naive patients with mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Leucovorin / administration & dosage*
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxonic Acid / administration & dosage*
  • Oxonic Acid / adverse effects
  • Survival Analysis
  • Tegafur / administration & dosage*
  • Tegafur / adverse effects
  • Treatment Outcome

Substances

  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Leucovorin