Chemotherapy for bile duct carcinoma in the light of adjuvant chemotherapy to surgery.

Chemotherapeutic regimens that markedly improve survival and quality of life in patients with bile duct cancer (cholangiocarcinoma) have not yet been developed. Currently, radical resection is the only potentially curative treatment modality for these patients. However, complete resection is often impossible and, even when achieved, is typically followed by metastasis and/or local recurrence. During the past 25 years, patients with cholangiocarcinoma have received chemotherapy in an attempt to improve their prognosis; effective methods are systemic administration, hepatic arterial infusion, and intraductal infusion. 5-fluorouracil, adriamycin, mitomycin C, and cisplatin remain the agents used most frequently (either singly or in combination) for treating cholangiocarcinoma. In particular, 5-fluorouracil has been a component of most chemotherapy regimens for bile duct cancer. However, regardless of the administration scheme, results from the use of 5-fluorouracil as a single agent have been disappointing. Recent phase II (albeit small-population) trials that addressed the biochemical modulation of 5-fluorouracil in combination with methotrexate, leucovorin, cisplatin, interferon, or mitomycin C yielded better results than did a classic (combination of 5-fluorouracil, adriamycin, and mitomycin C) FAM regimen. Hepatic arterial infusion chemotherapy was associated with the highest response rate and survival in patients with localized cholangiocarcinoma (localized in the liver, with no extra-hepatic metastasis); however, these results need to be confirmed in large, randomized trials. Studies regarding intraductal chemotherapy for patients with obstructive jaundice are still in the preliminary stages; therefore, no associated benefit could be ascertained. The present review discusses current chemotherapy regimens for bile duct cancer and outlines possible future clinical investigations.