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


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%).


CONCLUSIONS
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.
Koizumi
W
W
Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa. Electronic address: koizumi@med.kitasato-u.ac.jp.
Boku
N
N
Division of Gastrointestinal Oncology, Shizuoka Cancer Centre, Shizuoka.
Yamaguchi
K
K
Department of Gastroenterology, Saitama Cancer Centre, Saitama.
Miyata
Y
Y
Department of Gastroenterology, Saku Central Hospital, Nagano.
Sawaki
A
A
Department of Gastroenterology, Aichi Cancer Centre Hospital, Aichi.
Kato
T
T
Department of Surgery, Minoh City Hospital, Osaka.
Toh
Y
Y
Department of Gastroenterological Surgery, National Kyushu Cancer Centre, Fukuoka.
Hyodo
I
I
Department of Gastroenterology, University of Tsukuba, Ibaraki.
Nishina
T
T
Department of Internal Medicine, National Hospital Organization Shikoku Cancer Centre, Ehime.
Furuhata
T
T
First Department of Surgery, Sapporo Medical University School of Medicine, Hokkaido.
Miyashita
K
K
Department of Surgery, National Hospital Organization Nagasaki Medical Centre, Nagasaki.
Okada
Y
Y
Department of Internal Medicine, Nakabaru Hospital, Fukuoka, Japan.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002955:Leucovorin