A phase II study of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer.

Abstract

Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (1-week administration followed by 1-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer. Patients with previously untreated advanced or relapsed gastric cancer who had measurable lesion(s) were enrolled. Paclitaxel was administered intravenously at a dose of 120mg/m(2) on day 1 and oral S-1 was given twice daily (BSA<1.25m(2), 80mg/day; 1.25≤BSA<1.50m(2), 100mg/day; 1.50m(2)≤BSA, 120mg/day) on days 1-7 followed by a drug-free interval of 1week every 14-day cycle. Forty-four patients (M/F=33/11) were enrolled. A total of 277 chemotherapy cycles were administered, with a median of six cycles per patient (range 1-12), and 19 (43.2%) patients received up to seven cycles. The assessed overall response rate was 38.6 with 38.6% partial response in 17 patients, 45.4% stable disease in 20 patients, and 13.6% progressive disease in six patients. Thirty-four patients (77.3%) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.2months (95% CI 4.08-6.39months) and 12.2months (95% CI 8.81-15.60months). The major hematological toxicities were included grade 3 leucocytopenia in two patients (4.5%), grade 3 neutropenia in 14 patients (40.9%), and grade 4 neutropenia in four patients (9.0%). Two patients (4.5%) suffered grade 1 febrile neutropenia. All grade of the non-hematological toxicities, such as nausea, vomiting, alopecia, and diarrhea, held the proportion of 54.5% (grade 3/4, 4.5%), 31.8, 95.4, and 18.1% (grade 3/4, 2.2%), respectively. Biweekly S-1 and paclitaxel (SPA regimen) combination therapy had promising activity with acceptable adverse toxicities. SPA regimen was easily implemented, and more patients received second-line chemotherapy. It deserved to conduct a well-designed randomized phase III study to compare this regimen with S-1-based combination treatment.