Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer.
PURPOSE: To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. RESULTS: One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. CONCLUSION: These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.