Gemcitabine With/Out Capecitabine in Locally Advanced, Unresectable, or Metastatic Biliary Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven adenocarcinoma of the biliary tree (intra- and extra-hepatic biliary ducts or gallbladder)
• Locally advanced, unresectable, or metastatic disease
• Patients with pathologically confirmed metastatic adenocarcinoma consistent with biliary primary with clinical documentation of gallbladder or biliary tree involvement and no evidence of another primary adenocarcinoma are eligible
• Must have evidence of disease but measurable disease is not required
• Chest x-ray and/or CT scan of the chest, CT scan or MRI of the abdomen, and other radiological examination to document all disease sites have been done within 28 days prior to randomization
• No repeat scan needed if a negative scan was performed within 35 days prior to randomization
• Patients who have only one site of disease located inside a previous radiotherapy field are eligible
• Lesions within a previous radiotherapy field may be considered measurable if documented ≥ 20% increase in size
• If the lesion size increase has not been documented since the completion of radiotherapy, and the lesion is still present (i.e. not CR), the lesion is considered evaluable for this trial
• Patients with biliary duct obstruction are eligible provided all of the following criteria are met:
• Treatable, clinically relevant obstruction
• Obstruction has been relieved by internal endoscopic drainage/stenting, palliative bypass surgery or percutaneous drainage prior to trial entry
• No ampullary carcinomas (i.e., arising from the ampulla of Vater)
• No central nervous system (CNS) metastases, including active, progressive brain or leptomeningeal metastases
• Patients with focal neurological symptoms must have had a CT scan to rule out CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Minimum life expectancy of 12 weeks
• Able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in one of the validated languages
• Must be able to swallow and retain oral medication
• Hemoglobin > 90 g/L
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin < 3 times upper limit of normal(ULN)
• AST and/or ALT ≤ 5 times ULN
• Liver function tests stable and < 3 times ULN
• Serum creatinine < 160 µmol/L OR creatinine clearance > 60 mL/min
• Negative pregnancy test
• Fertile patients and their partners must agree to use adequate contraception prior to study entry, throughout the study, and for a period of 4 weeks after cessation of protocol therapy
• Patients must be accessible for treatment and follow-up
• No known dihydropyrimidine dehydrogenase deficiency
• No known hypersensitivity to gemcitabine or capecitabine
• No other active medical condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy, including, but not limited to, any of the following:
• Unstable angina
• Uncontrolled arrhythmia
• Heart failure
• No other condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
• No other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 5 years

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for advanced or metastatic disease unless used in the following circumstances:
• Fluorouracil or gemcitabine given concurrently with radiotherapy as a radiosensitizer, completed more than 3 months prior to randomization
• Fluorouracil given as adjuvant treatment following surgery, completed at least 1 year prior to randomization
• No major surgery within 4 weeks of randomization
• No prior treatment with another investigational agent within 2 weeks of randomization
• At least 4 weeks from randomization since completion of prior radiotherapy and recovered
• Patients may be randomized within the required 4 weeks if short course (< 5 fractions) of non-myelosuppressive radiotherapy was given
• Concurrent palliative radiation to a known site of bone metastasis allowed provided that the criteria for disease progression are otherwise not met
• No other concurrent anti-cancer therapy (cytotoxic, biological/immunotherapy or radiotherapy other than for known bone metastases as specified above)
• No other concurrent investigational drug therapy