The previous phase II study of the oral S-1 plus oral Leucovorin (LV) (2 weeks on/2 weeks off) for patients with untreated metastatic colorectal cancer (mCRC) have shown to be effective, but the grade 3 toxic effects (diarrhea, stomatitis, and anorexia) were observed with relatively high frequency. In this phase II study, we modified the administration schedule of S-1 plus LV regimens for well-tolerated toxic effects and evaluated the efficacy.Methods
Patients were eligible as follows: histologically confirmed adenocarcinoma, age ≥ 20, ECOG PS 0-1, no prior chemotherapy, at least one measurable lesion by RECIST ver1.0 criteria, adequate organ function, and written informed consent. S-1 (40-60 mg b.i.d.) and LV (25 mg b.i.d.) were orally administered for 1 week, followed by 1 week rest period. Treatment was repeated until the onset of disease progression or unacceptable adverse events occurred. The primary end point was the response rate (RR), and the secondary end points were efficacy and safety. This trial was supported by Taiho Pharmaceutical CO., Ltd. ClinicalTrials.gov Identifier: NCT00891332Results
From October 2008 to June 2009, 73 patients were enrolled in Japan and China. Of the eligible 71 patients, the median age was 60 (range 27-84), male/female was 38/33, PS: 0/1 was 39/32, and Japan/China was 32/39. RR as primary end point was 53.5% (95% CI, 41.3–65.5), and disease control rate was 83.1%. With a median follow-up period of 26.4 months, the median progression-free survival was 6.5 months. Median overall survival was 24.3 months with the survival rate of 77.5% at 1 year and 53.2% at 2 years. The incidences of grade 3 adverse drug reactions were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8%, neutropenia 9.7%, and there was no treatment-related death.Conclusions
The modified treatment schedule of S-1 plus LV (1w on/ 1w off) showed similar good efficacy and better tolerability compared with the previous treatment schedule (2w on/ 2w off). This therapy showed promising activity in patients with untreated mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs.