Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604)

Abstract

e15567 Background: Although an adjuvant chemotherapy with S-1 has become the standard treatment for stage II-III gastric cancer (GC) patients (pts) after curative D2 gastrectomy in Japan, the survival benefit for stage III pts obtained by S-1 is considered to be modest. S-1 plus docetaxel has shown a good response rate of 56% with prolonged median overall survival (OS) of 14.3 months in pts with advanced GC. This phase II study evaluated the feasibility and safety of adjuvant S-1 plus docetaxel for stage III GC pts after R0 resection. Methods: Patients with curatively resected pathological stage III GC receiving D2 dissection, age 20–80 years, performance status < 1, no prior adjuvant treatment, adequate organ function, and informed consent were given S-1 (80 mg/m2/day) orally for consecutive 2 weeks plus docetaxel (40 mg/m2) intravenously on day 1, repeated every 3 weeks. The treatment was started within 45 days after gastrectomy, and repeated for 4 cycles, followed by S-1 monotherapy until 1 year after surgery. Study endpoints included feasibility of the 4 cycles of S-1 plus docetaxel as primary, and safety, progression free survival (PFS), and OS as secondary. Sample size was set to be 50, which was determined to reject the feasibility of 50% under the expectation of 75% with power of 90% and two-sided α of 5%. Results: Fifty-three pts, 42 males and 11 females with a median age of 65 years, were enrolled between 5/2007 and 8/2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. Planned 4 cycles of treatment were delivered to 41 out of 53 pts, with the feasibility of 77.4% (95% CI 63.8–87.7%, P<0.001). Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Conclusions: Adjuvant S-1 plus docetaxel was well-tolerated and showed good compliance. Although follow-up is ongoing on survival, this regimen could be a candidate of future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after curative D2 gastrectomy. No significant financial relationships to disclose.