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

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.

• Authors: Tadashi Uwagawa, Taro Sakamoto, Kyohei Abe, Norimitsu Okui, Daigo Hata, Hiroaki Shiba, Yasuro Futagawa, Keisuke Aiba, Katsuhiko Yanaga
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 75 Issue 1 Pg. 191-6 (Jan 2015) ISSN: 1432-0843 [Electronic] Germany
• PMID: 25422155 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

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

Topics

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