Oxaliplatin and Bolus-Modulated 5-Fluorouracil as a Second-Line Treatment for Advanced Pancreatic Cancer: Can Bolus Regimens Replace FOLFOX When Considered for Second Line?

Objective. Comparing activity of 2 regimens combining oxaliplatin to bolus modulated fluorouracil as second line treatment in advanced pancreatic adenocarcinoma pretreated with gemcitabine-containing schedule. Methods. Forty eight patients with advanced pancreatic adenocarcinoma were randomly assigned to receive either FU 500 mg/m2 IV bolus weekly ×6 weeks plus leucovorin 500？mg/m2 IV weekly for 6 weeks during each 8-week cycle plus oxaliplatin 85？mg/m2 IV on weeks 1, 3, and 5 of each 8-week (FLOX) OR receive weekly intravenous infusions of oxaliplatin 40？mg/m2, 5-FU 500 mg/m2, and leucovorin 250？mg/m2 (3 weeks on, 1 week off). Results. Non progression(PR+SD) was found in 33.5% for first regimen and 29% for second regimen, and 37.5% had clinical benefit (FLOX regimen) compared to 50% in 3-weeks regimen. The median TTP was 3.9,4 months respectively. Median OS was 8, 9 months for both regimens. Only one case in 3-weeks arm suffered from grade IV diarrhea. Two cases > grade 2 neutropenia were observed; one in each treatment groups. Grade 3 anemia was recorded in 3 patients (2 in FLOX arm, one in 3-weeks arm). Conclusions. Both regimens showed encouraging efficacy, acceptable toxicity, and clinical benefit. 1. Introduction Due to the fact that the majority of pancreatic cancers are unresectable upon diagnosis, curative intent is rarely a goal of treatment, rather increasing survival, time to progression, and quality of life are more realistic goals. Without treatment, median survival for patients with an advanced stage of disease ranges from 3 to 4 months, whereas in patients receiving chemotherapy with single-agent gemcitabine, median survival times between 4.9 and 7.2 months have been reported in randomized phase III studies [1]. Gemcitabine has been the solo player in the field of pancreatic cancer, treatment after replacing 5-FU since 1997, and is still regarded as one standard of care for the first-line systemic chemotherapeutic treatment of patients with advanced pancreatic cancer worldwide. So far, only two randomized phase III trials have demonstrated a significant prolongation of survival with the use of gemcitabine-based combination therapy with either erlotinib or capecitabine [2]. Eventually, progression will occur and the real challenge will be how to treat a patient with advanced pancreatic cancer failing to respond or progressing after gemcitabine. There is no evidence-based treatment recommendation for these patients. The National Comprehensive Cancer Network guidelines for pancreatic adenocarcinoma currently recommend second-line