Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate

Purpose This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer. Patients and Methods IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m(2) and irinotecan 100 mg/m(2) given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety. Results In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% Cl, 4.7 to 7.5 months) and 6.6 months for GEM (95% Cl, 5.2 to 7.8 months; log-rank P = .789). Tumor response rates were 16.1% (95% Cl, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% Cl, 1.9% to 8.6%) for GEM (chi(2) p <. 001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P = .352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar. Conclusion IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival. (C) 2004 by American Society of Clinical Oncology.