Phase I/II Study of S-1 Plus Cisplatin Alternating With S-1 Plus Docetaxel in Patients With Advanced Gastric Cancer.

OBJECTIVES

To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with advanced gastric cancer, we conducted a phase I/II study to determine the maximum tolerated dose and recommended dose, and evaluate efficacy and toxicity.

MATERIALS AND METHODS

Patients with histologically confirmed unresectable and recurrent gastric cancer were enrolled in this study. Cisplatin was administered on day 1 and the dose escalated by 10 mg/m from a starting dose of 40 mg/m in the phase I part. S-1 was given orally at 80 mg/m on days 1 to 14 and docetaxel at 40 mg/m on day 22 in combination with S-1 80 mg/m on days 22 to 35. The treatment was repeated every 6 weeks. The primary endpoint of the phase II analysis was the response rate.

RESULTS

Nine patients entered the phase I and 24 the phase II part. Because 50% of patients (3/6) developed dose-limiting toxicities in the phase I part, the maximum tolerated dose of cisplatin was presumed to be 50 mg/m. Therefore, the estimated recommended dose of cisplatin was 40 mg/m; 27 patients received that dose. The response rate was 59.3% (95% confidence interval, 40.8-77.8) and the median follow-up 26.2 months. The median progression-free survival was 7.9 months and the median overall survival 18.6 months. The most common grade 3/4 toxicities were neutropenia (59.3%), leucopenia (37.0%), and anemia (29.6%). These toxicities were tolerable and manageable.

CONCLUSION

This alternating treatment seems to have promising activity with tolerable toxicities in the first-line treatment of patients with advanced gastric cancer.