Phase II study of 2-week TS-1 administration followed by 1-week rest for gastric cancer

TS-1 monotherapy with 4-week administration followed by 2-week rest is used as the community standard treatment for metastatic gastric cancer in Japan. However, according to a postmarketing survey, the percentage of patients who received three or more courses was only 44.6%; for the reasons of discontinuation due to exacerbation of symptoms or adverse reactions during the first or second course. Therefore, we conducted the phase II study of 2-weeks administration with TS-1 followed by a 1-week rest against metastatic gastric cancer, aiming for mitigation of adverse reactions without reduction of antitumor effect.

Thirty-five patients were enrolled between 2001 and 2003 at nine institutes in Japan. One cycle of TS-1 treatment whose dosage was 80 mg/m2/day consisted of administration for 2 weeks followed by a 1-week rest. The primary endpoint was overall response rate and the secondary endpoints were safety and feasibility.

There were 6 PRs, 13 NCs, 11 PDs, and 5 patients were not evaluable (NE), yielding a response rate of 17%. The median survival time of all patients was 290 days. Severe adverse Grade 3 or 4 reactions were observed in 8 (23%) patients. The rate of patients who received six or more courses was 43%. The cumulative rate of the relative total administration days was 93%.

We concluded that the schedule of TS-1 administration for 2 weeks followed by a 1-week rest might not be superior to the conventional schedule (4 weeks on and 2 weeks off) with regard to the antitumor effect, adverse reactions and prolonged medication, although it was acceptable from the point of view of survival.