A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201

Abstract

4506 Background: The role of radiation therapy (RT) as part of treatment for pancreatic cancer is uncertain in the post-gemcitabine era. The primary endpoint of this trial was to evaluate the impact upon overall survival for the combination of RT plus gemcitabine (G) versus G alone in locally unresectable pancreatic cancer. Methods: Patients (pts) with histologically proven, locally unresectable pancreatic adenocarcinoma, PS <2, without prior chemotherapy or radiation therapy were eligible. Pts were randomized to ARM A: G alone (1,000 mg/m2 weekly x 3 every 4 weeks) for 7 cycles, or ARM B: RT (50.4 GY in 28 fractions) plus G (600 mg/m2 weekly x 6) followed by 5 cycles of G alone (1,000 mg/m2 weekly x 3 every 4 wks). With a planned sample size of 316 eligible pts, the trial was designed to have an 88% power to detect a 50% improvement in median overall survival from 8 to 12 mos (one-sided log-rank test; significance level = 0.025). Pts were stratified by PS (0 vs.1) and weight loss in prior 6 mos (>10% vs. < 10%). Quality of life (using FACT-Hep) was prospectively measured. Results: From April, 2003 to December, 2005, 74 pts were enrolled. The study was closed early because of slow accrual. Three pts were ineligible because of metastatic disease. Five pts not receiving assigned therapy (metastasis noted during RT planning-2; clinical deterioration-2; withdrew consent-1) are included for survival. Grade IV toxicity, principally gastrointestinal and hematologic, was more common in ARM B (5.7% vs 41.2%; p<0.0001). Objective responses were observed in 2.7% (95% CI [0.09%, 14.1%]) and 8.8% (95% CI [1.9%, 23.7%]) in ARM A and ARM B respectively; the corresponding progression free survivals were 6.1 vs. 6.3 mos (p=0.34). All 71eligible pts have now died (early deaths: ARM A-3, ARM B-1). The MST were 9.2 (95% CI [7.8, 11.4]) and 11.0 (95% CI [8.4, 15.5]) mos for the two arms respectively (p=0.044 two sided stratified log-rank test; one-sided p=0.022). Conclusions: Gemcitabine plus radiotherapy has increased, but generally manageable, toxicities compared to chemotherapy alone. Gemcitabine plus involved field RT is associated with an improved overall survival compared to gemcitabine alone for localized, unresectable pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly