Intra-arterial Infusion of 5-Fluorouracil, Leucovorin, Epirubicin and Carboplatin (FLEC regimen) in Unresectable Pancreatic Cancer: Results of a Ten-year Experience

The final results of a new regimen given intra- arterially for unresectable pancreatic cancer (UPC) are presented. Patients and Methods: From January 1994 to January 2006, 5-fluorouracil 1,000 mg/m 2 , leucovorin 100 mg/m 2 , epirubicin 60 mg/m 2 and carboplatin 300 mg/m 2 were administered every 3 weeks into the celiac axis (CA) angiografically (FLEC regimen) to 211 patients with UPC. Results: Seven hundred and sixty-four cycles were administered. Grade 3-4 hematological toxicity was observed in 24%; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; grade 3 alopecia in 15%. One sudden death, a pre- infarction angina and a transitory ischemic attack were observed. No complications related to the angiographic procedure took place, but three tunica intima dissections of the iliac artery occurred; 7.6% of patients with partial responses and 50.7% with stable disease were observed. Two hundred and one patients have died; median overall survival was 9.2 months: 10.5 and 6.6 for stage III and IV, respectively. Conclusion: The FLEC regimen given intra-arterially is well- tolerated and effective in patients with UPC. Carcinoma of the exocrine pancreas is the fifth leading cause of death from malignant disease in Western countries. The diagnosis is generally late and only 10-20% of the patients are in stage I or II at the time of diagnosis. Ninety- nine percent of patients with pancreatic adenocarcinoma die of their disease, with an overall 5-year survival rate of less than 4% (1). Late diagnosis, chemoresistance and radioresistance of pancreatic cancer are the main reasons for the poor therapeutic results (2). Currently, standard treatment for patients with unresectable pancreatic adenocarcinoma is systemic gemcitabine (GEM), with only a small, but significant advantage in terms of survival and clinical benefit, if compared with best supportive care (3). Up to now, no combination of GEM with another chemotherapeutic agent has been shown to be clearly superior to GEM alone. Recently, a four-drug regimen (gemcitabine, cisplatin, epirubicin and 5-fluorouracil; FLEC regimen) has been associated with improvement in both tumor response rate and progression-free survival when compared with gemcitabine alone, with a small, but significant improvement in overall survival (OS) (4). A number of ongoing trials are exploring the potential benefit of GEM with novel agents, such as antibodies to the epidermal growth factor receptor and vascular endothelial growth factor. In 2005, a randomized phase II study comparing GEM alone versus GEM plus erlotinib (an oral epidermal growth factor receptor tyrosine kinase inhibitor) had shown a statistical improvement in survival for the combination treatment (5). Intra-arterial chemotherapy for the treatment of pancreatic cancer has been evaluated and preliminary results have indicated that pancreatic cancer is dose dependently sensitive to regional chemotherapy and that the method offered interesting response rates, survival and quality of life in some uncontrolled small trials (6-11). This year, the FLEC regimen with or without systemic GEM as