Gemcitabine is considered the golden standard treatment for unresectable pancreatic
adenocarcinoma. Intra-arte-rial
drug administration had shown a deep rationale with some interesting results. In a multicenter phase III trial, we compared
gemcitabine given weekly with a combination of 5-fluoruracil,
leucovorin,
epirubicin,
carboplatin (
FLEC) administered intra-arteriously as first-line
therapy in unresectable pancreatic
adenocarcinoma. Patients were randomly assigned to receive
gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or 5-fluoruracil 1,000 mg/m2,
leucovorin 100 mg/m2,
epirubicin 60 mg/m2,
carboplatin 300 mg/m2 infused bolus intra-arteriously at three-weekly interval for 3 times. The primary end point was overall survival, while
time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated
gemcitabine and 71 were allocated
FLEC intra-arterially. Patients treated with
FLEC lived for significantly longer than patients on
gemcitabine (p=.036). Survival at 1 year was increased from 21% in the
gemcitabine group to 35% in the
FLEC group. Median survival was 7.9 months in the
FLEC group and 5.8 months in the
gemcitabine group. Median
time to treatment failure was longer with
FLEC (5.3 vs 4.2 months for
FLEC vs
gemcitabine respectively; p=.013). Clinical benefit was similar in both groups (17.9% for
gemcitabine and 26.7% for
FLEC; p=NS). CT-scan partial response was similar in both group (5.9% for
gemcitabine and 14% for
FLEC; p=NS). Toxicity profiles were different. Compared with
gemcitabine,
FLEC regimen given intra-arteriously, improved survival in patient with unresectable pancreatic
adenocarcinoma.