Phase I trial of S-1 every other day in combination with gemcitabine/cisplatin for inoperable biliary tract cancer

Cancer Chemother Pharmacol. 2015 Jan;75(1):191-6. doi: 10.1007/s00280-014-2636-0. Epub 2014 Nov 25.

Abstract

Purpose: To date, gemcitabine-based or fluoropyrimidine-based regimens are recommended for unresectable advanced biliary tract cancer. Then, we conducted a phase I study of gemcitabine/cisplatin and S-1 that is an oral fluoropyrimidine. The aim of this study was to determine the dose-limiting toxicity (DLT), maximum-tolerated dose, and a recommended phase II dose of S-1. Response was assessed as a secondary endpoint.

Patients and methods: Patients who have been diagnosed with unresectable or postoperative recurrent biliary tract cancer received cisplatin (25 mg/m² i.v. for 120 min) followed by gemcitabine (1,000 mg/m² i.v. for 30 min) on days 1 and 8, and oral S-1 on alternate days; this regimen was repeated at 21-day intervals. A standard '3 + 3' phase I dose-escalation design was adopted. This study was registered with University hospital Medical Information Network (UMIN) Center in Japan, number UMIN000008415.

Results: Twelve patients were evaluable in this study. No patients developed DLTs. Recommended dose of S-1 was 80 (<1.25 m²), 100 (1.25 ≤ 1.5 m²), and 120 mg (1.5 m²≥) per day. One patient could achieve conversion to curative surgery.

Conclusion: This phase I study was performed safely and demonstrated encouraging response.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects
  • Prodrugs / therapeutic use
  • Survival Analysis
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Drug Combinations
  • Prodrugs
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Cisplatin
  • Gemcitabine

Associated data

  • JPRN/UMIN000008415