Results of a phase I study of fixed dose rate gemcitabine /irinotecan (FIGI)

Abstract

2112 Background: Based on the activity of combined gemcitabine (gem)/ irinotecan (irino), we performed a phase I/PK study using Fixed Dose Rate (FDR) Infusion gem. The primary objectives were DLT and RPTD of irino combined with FDR Infusion gem at 10mg/m2/min(FIGI). Secondary objectives included the evaluation of antitumor activity as well as the PK and pharmacodynamic interaction of this combination. Methods: Pts with advanced cancer, adequate organ function, and PS of 0–1 were eligible. Gem and irino were given on days 1 and 8 q21d according to the dose levels below. Gem was infused over the time noted. Pts were followed with weekly CBC's and CT scans q 2 cycles. Results: 17 pts with, med age 54 (34–67 yrs), and med 1 prior regimen were enrolled, including 6 pancreatic, 4 gastric/GEJ, 3 colorectal and 1 pt each with anal, cholangio, esophageal, and primary peritoneal carcinoma. All are evaluable for toxicity, 16 for response. 1 pt at DL4 is currently being treated. The MTD and RPTD have not yet been reached; however, many pts required dose reductions and delays. Pts were treated for a med of 6 cycles. Observed toxicity was gr 1–2 including fatigue, abd pain, muscleoskeletal pain, and nausea/vomiting. There were 12 episodes of gr3 and 2 gr4 non-heme toxicity. Gr 3/4 heme toxicities are listed below. DLT has not been observed with 2 deaths unrelated to protocol therapy. 6 pts have achieved a response; CR in 4 (2 gastric, 1 pancreatic and primary peritoneal cancer) and PR in 2 (G-E junction and pancreatic). 4 pts had stable disease. Conclusion: “FIGI” is a well-tolerated and effective regimen in pts with advanced GI malignancies. Gem by FDR infusion does not appear to substantially increase toxicity compared to “IrinoGem” (100mg/m2 & 1000mg/m2 over 30min). Although MTD has not been reached; a dose of Gem/Irino 900/90mg/m2 appears to be best tolerated in pre-treated pts. A phase II study to further evaluate the activity of this regimen in UGI cancer is planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly