S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma

OBJECTIVES:

• Determine the response rates (confirmed complete and partial responses) in patients with unresectable, locally advanced or metastatic gallbladder cancer or cholangiocarcinoma treated with gemcitabine and capecitabine.
• Determine the overall survival of patients treated with this regimen.
• Determine the quantitative and qualitative toxic effects of this regimen in these patients.
• Determine the feasibility of accruing patients with these disease sites.
• Evaluate, preliminarily, relevant prognostic markers in these disease sites and the prognostic implications as predictors of survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14 and gemcitabine IV over 100 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within approximately 10-20 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed gallbladder cancer or cholangiocarcinoma

• Locally advanced or metastatic disease that is unresectable
• Eligible subtypes:

• Adenocarcinoma, intestinal type
• Adenocarcinoma, not otherwise specified (NOS)
• Papillary carcinoma
• Clear cell adenocarcinoma
• Mucinous carcinoma
• Signet ring cell carcinoma
• Squamous cell carcinoma
• Adenosquamous carcinoma
• Small cell carcinoma
• Undifferentiated carcinoma
• Carcinoma, NOS

OR

• Histologically confirmed adenocarcinoma of a metastatic site with clinical documentation* of gallbladder or bile duct involvement and no evidence of another primary

NOTE: *If clinical documentation of gallbladder or bile duct involvement is not possible due to removal of the organ, a clinically and/or radiographically consistent picture plus pathologic findings from the metastatic site consistent with cholangiocarcinoma are allowed

• Measurable disease located outside prior radiotherapy port
• No carcinoid tumors or sarcomas

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) no greater than 2.5 times ULN (5 times ULN if liver metastasis is present)

Renal:

• Creatinine clearance at least 30 mL/min

Cardiovascular:

• No clinically significant cardiac disease that is not well controlled by medication
• No congestive heart failure
• No symptomatic coronary artery disease
• No cardiac arrhythmias
• No myocardial infarction within the past 12 months

Gastrointestinal:

• Able to swallow and/or receive medications via gastrostomy feeding tube
• No intractable nausea or vomiting
• No malabsorption syndrome

Other:

• No severe reaction to fluoropyrimidine therapy or known hypersensitivity to fluorouracil
• No other malignancy within the past 5 years except:

• Adequately treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Adequately treated stage I or II cancer currently in complete remission
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior neoadjuvant or adjuvant immunotherapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
• No concurrent immunotherapy

Chemotherapy:

• Prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
• No other concurrent chemotherapy

Endocrine therapy:

• Prior neoadjuvant or adjuvant hormonal therapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
• No concurrent hormonal therapy

Radiotherapy:

• See Disease Characteristics
• See Chemotherapy
• Recovered from prior radiotherapy
• Prior neoadjuvant or adjuvant radiotherapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
• No prior radiotherapy to 25% or more of bone marrow
• No concurrent radiotherapy except for palliation of metastatic sites not considered target lesions

Surgery:

• At least 2 weeks since prior surgery for this malignancy and recovered

Other:

• No prior treatment for metastatic disease
• No other concurrent therapy for this cancer