Gemcitabine (Gem), cisplatin (Cis) and radiation therapy (RT) for patients with locally advanced pancreatic adenocarcinoma (ACA): A North Central Cancer Treatment Group (NCCTG) phase II study

Abstract

4121 Background: In vitro studies suggest that low dose GEM sensitizes cells to RT for 48 hours following exposure. CIS is a radiation sensitizer and may result in synergistic cytotoxicity when combined with GEM. This phase II study was conducted to determine the efficacy of RT with concomitant GEM and CIS in patients (pts) with locally advanced pancreatic ACA. Methods: GEM and CIS were delivered twice weekly during the first 3 weeks of RT using the phase I study MTD of GEM 30 mg/m2 and CIS 10 mg/m2. RT dose was 45 Gy (180 cGy/fx) to the primary tumor and regional nodes with a 5.4 Gy boost to the gross tumor volume. Four weeks post-RT, pts received GEM 1000 mg/m2 3 weeks out of 4 for 12 weeks. Survival at 12 months (mos) was the primary endpoint with secondary endpoints of time to progression (TTP), toxicity and quality of life(QOL). Planned accrual was 45 pts with a requirement that 13 of 20 or 23 of 45 survive 12 mos as evidence of promising activity. Results: 48 pts were enrolled in 22 mos; 20 were evaluable for survival endpoints. Survival at one year was 30% (6/20, 95% CI: 15–53%), median survival was 8.8 mos (95% CI: 5.9–13) and median TTP was 7.1 mos (95% CI: 2.6–8.2). Overall QOL scores (SDS, LASA) did not significantly change over time, but 5 individual QOL subscales significantly improved (insomnia, outlook, depression (SDS); frequency of pain (SDS, LASA)). 47 pts were evaluable for adverse events (AEs). 42 (89%) and 12 pts (26%) experienced at least one grade 3+ or grade 4+ AE, respectively, with one grade 5 AE (melena). Frequently occurring grade 3+ AEs are shown below: Conclusions: Survival results in the initial 20 pts treated with GEM, CIS, and RT for locally advanced pancreatic ACA did not meet our predefined criteria for success. Future studies will focus on novel agents in addition to RT in this setting. Supported by Grant CA-25224. No significant financial relationships to disclose.