S1019 A Randomized Phase II Study Designed to Compare Toxicity and Dose Intensity Between Four-Week Versus Three-Week Schedule of Gemcitabine for Advanced Pancreatic Cancer

Abstract

Purpose: The aim of this phase II study is to compare toxicity and dose intensity (DI) between four-week (4w) and three-week (3w) schedule of gemcitabine (GEM) for advanced pancreatic cancer (PC). Methods: Patients with histologically or cytologically proven locally advanced and/or metastatic PC were assigned to receive GEM in 4w schedule or 3w schedule. The protocol of GEM was as follows: 4w schedule (1,000mg/m2 on days 1, 8 and 15 of each 28-day cycle), 3w schedule (1,000mg/m2 on days 1 and 8 of each 21-day cycle). If grade 3 to 4 hematological toxicity (only a platelate count was defined = 50%, age between 20 and 80 years, and adequate organ function. Written informed consent was obtained from all patients. The primary endpoint was a compliance rate of protocol regimen within eight weeks after initiation of chemotherapy, which was defined as the proportion of patients without a dose reduction or a delay in administration of GEM. Secondary endpoints were DI, safety, response rate and overall survival. Results: A total of 90 patients (4w: 3w schedule= 45: 45) were enrolled between January 2006 and October 2008. Baseline patient and disease characteristics were similar in both schedules. Median age was 67 (range, 49-79) years in 4w schedule vs. 66 (range, 33-79) years in 3w schedule; p=0.67. KPS (70-80: 90-100%) was (4: 41) vs. (5: 40); p=0.99. Disease (locally advanced: metastatic) was (7: 38) vs. (7: 38); p=0.99. The eight week-compliance rate of protocol regimen was the same; 53.3% (24/45) in both schedules. However, median duration of accumulative rate for adverse events tended to be extended in 3w schedule; 35days (6-334) vs. 49 (6-414), p=0.20. Consequently, the mean received DI was equivalent in both schedules; 588 +/130 mg/m2/week vs. 550 +/116, p=0.14. Grade 3-4 neutropenia was a major adverse event in both schedules; 37.7% (17/ 45) vs. 35.5 (16/45); p=0.82, in contrast, thrombocytopenia was significantly increased in 4w schedule; 26.6% (12/45) vs. 4.4 (2/45); p=0.009. Tumor response rate was 14.2% (5/ 35) vs. 17.1(6/35); p=0.92, and the disease control rate (PR, SD) was 60.0% (27/45) vs. 62.2 (28/45); p=0.82. Median survival time was 206 (33-802) days vs. 250 (39-681); p= 0.84. Conclusions: These results support the efficacy and safety in 3w schedule of GEM for PC.