Folfox4 as a Rescue Chemotherapy for Gemcitabine-Refractory Pancreatic Cancer
ABSTRACT This phase II study assessed the efficacy and safety of FOLFOX4 as a rescue therapy in patients with gemcitabine-refractory pancreatic cancer.
The study included patients with advanced pancreatic cancer who had failed gemcitabine-based chemotherapy. FOLFOX4 was administered biweekly as follows: oxaliplatin, 85 mg/m² as a 2-hour infusion (day 1); leucovorin, 200 mg/m²/day as a 2-hour infusion (days 1 and 2); 5-fluorouracil, bolus 400 mg/m²/day and 600 mg/m²/day as a 22-hour infusion (days 1 and 2).
Forty-four patients received a total of 264 cycles of chemotherapy. There was 1 complete response (2.2%), 4 partial responses (9.1%), and 13 stable diseases (29.5%). The objective response rate was 11.4% and the tumor stabilization rate was 40.9%. The median time to progression was 9.9 weeks (95%CI: 8.2-11.5) and the median overall survival was 31.1 weeks (95%CI: 24.4-37.9). The common adverse events were hematologic toxicities: grade 3 or 4 neutropenia in 19 patients (43.2%), anemia in 9 patients (20.5%), and thrombocytopenia in 6 patients (13.5%). Grade 3 or 4 neuropathy occurred in 4 patients (9.1%).
In gemcitabine-refractory pancreatic cancer, FOLFOX4 showed encouraging activity and was generally well-tolerated. However, careful attention needs to be paid to hematologic toxicities.
[Show abstract] [Hide abstract]
ABSTRACT: While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.World Journal of Gastroenterology 03/2014; 20(9):2224-2236. DOI:10.3748/wjg.v20.i9.2224 · 2.43 Impact Factor