A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group Trial

Abstract

4105 Background: Survival of patients (pts) with locally advanced pancreas cancer is poor. Gemcitabine (GEM) is a known potent radiosensitizer with single agent activity in advanced disease. A phase I study conducted at IUCC, University of Michigan, and Fox Chase Cancer Center determined the MTD for GEM to be 600 mg/m2/week IV when administered with 5040 cGy external beam radiation (personal communication Dr. Steve Nicol). We conducted a phase II study to confirm safety and efficacy of GEM-radiation. Methods: Eligible pts had localized, biopsy-proven adenocarcinoma of the pancreas, deemed unresectable by CT scans and/or endoscopic ultrasound and confirmed by surgical evaluation. Pts received GEM 600 mg/m2 IV weekly, with concurrent radiotherapy, 180 cGy/day, 5 days/week, for a total of 5040 cGy, (part A ). Approx. 4 weeks after completion of combination therapy, pts without disease progression received GEM 1000mg/m2on days 1 & 8, of a 21-day cycle for 6 cycles (part B). Results: From April 2001-June 2003, 32 pts were enrolled on trial; 28 pts were evaluable (4 never received treatment). Pt characteristics: mean age 65 (36–78); PS 0/1= 18/10; and M:F= 15:13. Median follow-up is 7.8 mos. Twenty four (85.7%) pts completed part A of treatment. Grade 3 toxicities were principally hematologic and gastrointestinal, occurring in 12 pts (42.8%) and 10 pts (35.7%), respectively. Three (10.7%) pts had grade 4 toxicities (1 each for hyperbilirubinemia, infection and dyspnea). Six pts (21%) had a partial response, 16 pts (57%) had stable disease and 4 pts (14%) had progressive disease. Although not part of the study, 4 pts (14%) went on to surgical resection (findings: microscopic adenocarcinoma-1; extensive fibrosis-1; unresectable-2). The median time to progression was 6.3 mos (95% C.I. 4.5–7.4 mos). The one-year survival time is 31.1% (95% C.I.: 7.4%–54.8%). Median survival time was 7.9 mos (95% C.I. 6.6–17.1 mos). Conclusion: GEM/radiation has moderate toxicities and can be safely administered in the community setting. An Intergroup Phase III study comparing GEM alone versus GEM/radiation is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly