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

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.

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.

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%).

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.