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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

Phase 2
18 Years
80 Years
Not Enrolling
Biliary Tract Disease

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Trial Information

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.

Inclusion Criteria

Inclusion criteria:

1. Histologically proven carcinoma of the biliary tract, including gallbladder carcinoma
and cholangiocarcinoma. The disease should be either locally advanced to the extent
that curative surgery is impossible or with documented distant metastasis.

2. Bi-dimensionally measurable disease by physical examination or image study
(roentgenogram or computed tomography (CT) scan).

3. Age > 18 years. For patients older than 70 years of age, detailed evaluation of the
organ function reserves must be done before enrollment unto protocol treatment.

4. Karnofsky performance status> 60%

5. Adequate bone marrow reserves, defined as white blood cell (WBC)>4,000/ml, absolute
neutrophil count (ANC)> 1,500/ml, platelet> 150,000/ml.

6. Liver transaminases <5 times upper normal limits; total bilirubin <3 mg/dl; serum
creatinine < 1.5 mg/dl

7. Serum triglyceride level >70 mg/dl

8. No prior cytotoxic chemotherapy. Previous radiotherapy is allowed if the treatment
was completed at least 6 weeks before the enrollment onto this study.

9. Patients of childbearing age should have effective contraception during the study

10. All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional guidelines.

Exclusion criteria:

1. Patients who are receiving concurrent radiotherapy, chemotherapy or other
experimental therapy.

2. Patients who refuse port-A catheter implantation

3. Patients with brain or leptomeningeal metastases.

4. Patients who have significant cardiac arrhythmia or acute myocardial infarction
within 6 months before entry.

5. Patients who have major systemic diseases that the attending physicians considered
inappropriate for systemic chemotherapy.

6. Life expectancy less than 2 months.

7. Pregnant or nursing women may not participate. Women or men with reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method.

8. Patients who have previous malignancy except for the following: adequately treated
basal cell or squamous cell skin cancers, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or
any cancer from which the patient has been disease-free for 5 years.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the response rate of weekly gemcitabine plus high-dose 5-FU/leucovorin chemotherapy for patients with advanced or metastatic biliary tract cancer.

Principal Investigator

Ann-Li Cheng, PHD

Investigator Role:

Study Chair

Investigator Affiliation:

National Taiwan University Hospital


Taiwan: Department of Health

Study ID:




Start Date:

July 2002

Completion Date:

August 2012

Related Keywords:

  • Biliary Tract Disease
  • Biliary Tract Diseases
  • Carcinoma