A phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable biliary tract cancer.

Background: Many clinical trials have been conducted with gemcitabine- or 5-fluorouracil-based regimens as treatment for unresectable biliary tract cancer; however, the results remain unsatisfactory. Because further therapeutic improvements are required, we conducted a phase I study of arterial infusion chemotherapy using a combination of gemcitabine and 5-fluorouracil.

Methods: In the first 3 cohorts, patients were to receive an arterial infusion of gemcitabine 600, 800 or 1000 mg/m(2), respectively, over 30 min on days 1 and 15, plus a continuous arterial infusion of 5-fluorouracil 300 mg/m(2)/day on days 1-5 and 15-19. In the final cohort, patients were to receive an arterial infusion of gemcitabine 1000 mg/m(2) over 30 min on days 1 and 15, plus 5-fluorouracil 400 mg/m(2)/day on days 1-5 and 15-19.

Results: Eighteen patients were enrolled. In the final cohort, three of six patients experienced grade 3 non-hematological toxicities (cholecystitis, cellulitis and pneumonia). Thus, we determined the maximum tolerated doses of gemcitabine and 5-fluorouracil in arterial infusion chemotherapy to be 1000 and 400 mg/m(2), respectively.

Conclusion: This regimen of gemcitabine and 5-fluorouracil is tolerable and warrants further investigation in biliary tract cancer.