4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.
Multicenter Phase II Study of Gemcitabine and S-1 Combination Therapy (GS Therapy) in Patients With Metastatic Pancreatic Cancer