Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

Abstract

This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m À2 per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m À2 day À1 for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5 -16% and 2 -22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25 -101 weeks) for GEM and 26 weeks (range 16 -46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2 -65 weeks) and 18 weeks (range 4 -51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1 -101 weeks) and 30 weeks (1 -101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.

Triplet cytotoxic chemotherapy with gemcitabine, 5-fluorouracil and cisplatin for advanced pancreatic cancer

“…As 10 patients in the present study experienced early discontinuation, which is a major cause of shortened median survival time, this discrepancy between time-point survival rate and median survival time may indicate that the major drawback of this triplet GFP regimen is the difficulty of long-term maintenance rather than the efficacy of treatment. Also, this discrepancy may explain why the median OS time of the GFP regimen in the present study appears to be inferior to that of previous duplet regimens, such as the combination of gemcitabine with cisplatin (7.1-8.3 months) (12)(13)(14)29,36), gemcitabine with oxaliplatin (9.2 months) (37), and gemcitabine with fluoropyrimidine (6.7-10.3 months) (9,10,28,38).…”

Metastatic pancreatic cancer: Is gemcitabine still the best standard treatment? (Review)

“…In addition, the Italian Group for Clinical Oncology Research (GOIRC) evaluated the efficacy of gemcitabine in combination with or without continuous 5-FU infusion. This trial also failed to report a significant improvement of median OS (31 vs. 30 weeks) and median progression-free survival (PFS) (14 vs. 18 weeks), in the experimental arm (24).…”

An Updated Meta-analysis and System Review:is Gemcitabine+Fluoropyrimidine in Combination a Better Therapy Versus Gemcitabine Alone for Advanced and Unresectable Pancreatic Cancer?

“…There were no publication biasesdetected by Egger test for the studies in all of our analysis, in the primary endpoint of OS (t=0.74, p=0.474) and PFS (t=0.35, p=0.738) (Higgins et al, 2002;Higgins et al, 2003;Huai et al, 2013). Each article included in the composition of the funnel plot did not find significant bias (Berlin et al, 2002;Scheithauer et al, 2003;Ohkawa et al, 2004;Di Costanzo et al, 2005;Riess et al, 2005;Herrmann et al, 2007;Bernhard et al, 2008;Cunningham et al, 2009;Nakai et al, 2012;Ozaka et al, 2012;Ueno et al, 2013;Sudo et al, 2014).…”