Prospective Phase II Randomized Trial-Weekly Gemcitabine Plus High-Dose 5-Fluorouracil/ Leucovorin in the Treatment of Advanced or Metastatic Carcinoma of the Biliary Tract
5-FU has been the mainstay of chemotherapeutic agents for gastrointestinal malignancies.
The use of weekly 24-hour infusion of HDFL produces high clinical response in a variety of
cancers, including colorectal, gastric and breast cancers, with minimal chemotherapy-related
toxicity. Gemcitabine is a synthesized deoxycytidine analogue that is metabolized to dFdCTP
in tumor cells and results in inhibition of DNA synthesis and depletion of normal cellular
nucleotide pool. It has been shown to be active in the treatment of pancreatic cancer and
non-small cell lung cancer. Since the biliary tract and the pancreas share a common
embryonic origin and cancers from both sites are characterized by resistance to most
chemotherapeutic agents, we postulate that gemcitabine may also be effective for cancer of
the biliary tract. In our institution we have devised a regimen of weekly gemcitabine and
24-hour infusion of HDFL for patients with advanced or metastatic pancreatic adenocarcinoma.
In 18 evaluable patients, 2 achieved a partial response and 3 minor response. The median
duration of response was 4 months and the treatment-related toxicity was acceptable.
The eligibility criteria are patients with advanced or metastatic carcinoma of the biliary
tract who are not candidates for curative surgical treatment; good performance status; no
prior chemotherapy; clinical measurable tumor; good organ function and good compliance.
Each cycle of chemotherapy consists of 4 weeks. On days 1, 8 and 15, gemcitabine will be
given by 30-minute intravenous infusion and 5-FU and leucovorin by 24-hour continuous
intravenous infusion. The dose of gemcitabine will be 1000 mg/m2. The doses of 5-FU will be
2000 mg/m2 and leucovorin, 300 mg/m2. Treatment will continue until disease progresses or
prohibitive toxicity develops. For patients with complete response (CR), chemotherapy will
continue for 3 additional courses after the documentation of CR. Estimated time for
patient accrual is 3 years.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the response rate of weekly gemcitabine plus high-dose 5-FU/leucovorin chemotherapy for patients with advanced or metastatic biliary tract cancer.
Ann-Li Cheng, PHD
National Taiwan University Hospital
Taiwan: Department of Health