PHASE III RANDOMISED COMPARISON OF GEMCITABINE (GEM) WITH GEMCITABINE PLUS CAPECITABINE (GEM-CAP) IN PATIENTS WITH ADVANCED PANCREATIC CANCER

Abstract

Background: Both gemcitabine and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This study was designed to compare the survival of gemcitabine (GEM) with gemcitabine plus oral capecitabine (GEM-CAP). Methods: Patients with histological and proven advanced carcinoma of the pancreas were randomised to GEM (1000mg/m2 weekly ×7 q8 weeks, then 1 week rest, thereafter weekly ×3 q4 weeks) or to GEM-CAP (gemcitabine 1000 mg/m2 weekly ×3 q4 weeks and capecitabine 1660 mg/m2/day for 21 days followed by 7 days' rest). Treatment continued until disease progression or intolerable toxicities. The primary outcome measure was survival. Results: Between May 02 and Jan 05, 533 patients were randomised to GEM (n = 266) and GEM-CAP (n = 267) arms. Baseline characteristics were well balanced (GEM/GEM-CAP) with regards to median age (62/62), stage IVB disease (71%/70%) and WHO performance status (PS) 0-1 (82%/81%). At the time of this interim analysis in May 05, 373 (70%) deaths have occurred. GEM-CAP significantly improved overall survival over GEM alone (Hazard Ratio [HR]: 0.80; 95% CI: 0.65-0.98; p = 0.026). The median survival for GEM and GEM-CAP was 6 months and 7.4 months respectively and 1-year survival rates were 19% and 26% respectively. After adjusting for baseline stratification factors (disease extent and PS), the survival advantage for GEM-CAP remains (HR: 0.77; 95% CI: 0.63-0.95; p = 0.014). The objective response rates were 7% (0CR, 19PRs) and 14% (3CRs, 35 PRs) in GEM and GEM-CAP respectively (p = 0.008). Conclusions: There was a significant improvement in overall survival by the addition of capecitabine to gemcitabine and is the new standard of treatment.