Fixed dose-rate gemcitabine (GEM) infusion in advanced pancreatic (PDAC) and biliary tree (BTC) carcinoma: A phase II study

Abstract

4182 Background: Weekly GEM infused over 30 min is considered the standard of care for advanced PDAC and has activity in advanced BTC. However, a fixed dose-rate infusion at the rate of 10 mg/m2/min has theoretical pharmacokinetic advantages and may result in improved therapeutic efficacy. Methods: From April 2002 to September 2003, 40 advanced PDAC (n = 27) or BTC (n = 13) pts (median age: 63 yrs, range 45–77; M/F: 21/19; PDAC/BTC: 27/13; LA/Met: 9/31; PS 0/1/2: 18/15/7) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly x 3 q4 wks thereafter (FDR-GEM). All 40 patients and 427 treatment weeks were evaluable for toxicity, 38 patients had measurable/evaluable disease according to WHO criteria and were evaluable for response, 32 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 25 patients had elevated CA19.9 serum levels at entry. Results: Median number of treatment wks delivered was 6 (range 2–22); toxicity was mild with G3–4 neutropenia in 18/427 (4,2%) wks, G3 anemia and thrombocytopenia in 9/427 (2,1%) and 6/427 (1,4%) wks, respectively, G3 ASAT elevation in 5/427 (1,1%) wks, and G3–4 ALAT elevation in 16/427 (3,7%) wks. Six out of 38 evaluable pts had a PR, 7 had a MR, 13 had SD, and 12 had PD. ORR according to the intent-to-treat was 15% (95% CI 4–26%). A positive CBR was obtained in 14/32 (44%) pts. Seventeen out of 25 (68%) pts had a reduction in CA19.9 >25%. Median TTF and median TTP were 17 (95% C.I.: 13–22) and 19 (95% C.I.: 15–23) weeks, respectively. Median OS was 40 weeks (95% C.I.: 36–45) and 1-year actuarial survival rate was 25.8%. At multivariate analysis, PS 0–1 at entry and locally advanced disease were the only independent predictors of longer TTP and OS, while a reduction in circulating CA19.9 serum levels >75% was an independent predictor of longer TTP, but had no impact on OS. Conclusions: In terms of cost/benefit ratio, the results obtained with FDR-GEM compare favorably with those reported in the literature for GEM-based combinations and indicate that pharmacokinetically rationale GEM scheduling may improve its therapeutic index. No significant financial relationships to disclose.