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

Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3 weeks 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 120 mg/m² on day 1 and oral S-1 was given twice daily (BSA < 1.25 m², 80 mg/day; 1.25 ≤ BSA < 1.50 m², 100 mg/day; 1.50 m² ≤ BSA, 120 mg/day) on days 1–7 followed by a drug-free interval of 1 week 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, 5.2 months (95 % CI 4.08–6.39 months) and 12.2 months (95 % CI 8.81–15.60 months). 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.