Phase II trial of gemcitabine and irinotecan plus celecoxib in advanced adenocarcinoma of the pancreas

Abstract

4155 Background: Over expression of the cyclooxygenase-2 (COX-2) enzyme has been reported in 90% of patients (pts) with pancreatic cancer. COX-2 derived prostaglandins contribute to tumor growth through angiogenesis and COX-2 inhibitors have been shown to arrest the growth of pancreatic cell lines in vitro. Gemcitabine (Gem) and irinotecan (I) is an active regimen in pancreatic cancer. The aim of this study is to evaluate the efficacy and toxicity of Gem + I + celecoxib in advanced pancreatic cancer. Methods: Study eligibility included chemotherapy naïve pts with locally advanced inoperable or metastatic pancreatic cancer, measurable disease, and performance status 0–2. Tumor response was assessed by RECIST criteria with CT imaging every 3 cycles. CEA, CA 19–9, pain assessment and QOL assessment with the FACT-pa were performed with each cycle. Patients received Gem 1000mg/m2 and I 100mg/m2 days 1 and 8 of a 21 day cycle. Celecoxib was given at a dose of 400mg BID throughout the entire study. Toxicity was graded according to the NCI common toxicity criteria. Results: A total of 20 pts (median age 57) were enrolled of which 17 (8 local, 9 metastatic) were evaluable for response and 18 for toxicity. The most common Grade 3/4 toxicities included 9 neutropenia (50%), 7 anemia (39%), 3 diarrhea (17%), 3 fatigue (17%), 2 nausea (11%), 1 edema (6%), 1 thrombocytopenia (6%) and 1 UGI bleed (6%). There was one treatment related death due to neutropenic sepsis. To date there have been 3 PR (18%), 12 SD (70%), and 2 PD (12%). 9/13 pts (69%) who reported pain prior to beginning treatment had a significant improvement. A marked decrease in elevated baseline CA 19–9 and CEA was observed in 12/14 and 8/10 pts respectively. 13 pts (76%) reported an improvement in quality of life. The overall median TTP was 8 months (m) (10.5 m for local, 6 m for metastatic). Median OS was 13 m (>16 m for local, 9 m for metastatic) with a 1 year OS of 64%. 31% of the pts are approaching a two year survival. Conclusion: Gem + I + celecoxib is an active regimen with both objective responses and clinical benefit demonstrated by improvement in pain and quality of life, reduction in tumor markers, and a 1 year OS of 64%. Toxicities are manageable and include neutropenia, anemia, and diarrhea. No significant financial relationships to disclose.