Annals of Oncology Advance Access published online on October 14, 2009
Annals of Oncology, doi:10.1093/annonc/mdp371
Phase II study of S-1 plus leucovorin in patients with metastatic colorectal cancer
1 Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa
2 Division of Gastrointestinal Oncology, Shizuoka Cancer Centre, Shizuoka
3 Department of Gastroenterology, Saitama Cancer Centre, Saitama
4 Department of Gastroenterology, Saku Central Hospital, Nagano
5 Department of Gastroenterology, Aichi Cancer Centre Hospital, Aichi
6 Department of Surgery, Minoh City Hospital, Osaka
7 Department of Gastroenterological Surgery, National Kyushu Cancer Centre, Fukuoka
8 Department of Gastroenterology, University of Tsukuba, Ibaraki
9 Department of Internal Medicine, National Hospital Organization Shikoku Cancer Centre, Ehime
10 First Department of Surgery, Sapporo Medical University School of Medicine, Hokkaido
11 Department of Surgery, National Hospital Organization Nagasaki Medical Centre, Nagasaki
12 Department of Internal Medicine, Nakabaru Hospital, Fukuoka, Japan
* Correspondence to: Dr W. Koizumi, Department of Internal Medicine, Kitasato University School of Medicine, 2-1-1 Asamizodai, Sagamihara-shi, Kanagawa 228-8520, Japan. Tel: +81-42-7489111; Fax: +81-42-7485120; E-mail: koizumi{at}med.kitasato-u.ac.jp
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.
colorectal cancer, leucovorin, LV, phase II, S-1
Received for publication January 19, 2009. Revision received June 22, 2009. Accepted for publication June 23, 2009.