eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract
Gallbladder Cancer: Treatment & Medication
Updated: Jun 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Although complete surgical resection is the only therapy to afford a chance of cure, en bloc resections of the gallbladder and portal lymph nodes carry a high morbidity and mortality (similar to bile duct carcinoma). Adequate surgical margins may be difficult to achieve. The role of adjuvant radiation therapy is to control microscopic residual deposits of carcinoma in the tumor bed and regional lymph nodes. The rationale for radiation therapy with or without concurrent chemotherapy in patients with unresectable disease is to provide palliation of symptoms. Rarely, it may increase survival.
- The role of radiotherapy for carcinoma of the gallbladder is unclear because the available literature is derived from small, single institutional experiences over many years, with a variety of treatment methods used. Complicating this is the fact that only approximately 25% of patients with carcinoma of the gallbladder can undergo curative surgery.
- Even large institutions do not accrue more than single-digit numbers of patients per year, and many are not on protocol. Available reports contain small numbers of patients with incomplete reporting of technical treatment data, histological grading, and tumor extent. The literature is strongly biased by patient selection, and interpretation of the reports is difficult. Given these difficulties, the data support the following statements:
- Radiotherapy has been delivered in a variety of situations, including after curative resections with close or positive microscopic margins, gross macroscopic residual disease, and palliative debulking with bypass.
- Significant increases in survival rates have been reported after curative surgery is attempted and only microscopic residual disease remains. Survival in these patients after surgery alone ranges from 6-7 months and can be prolonged to longer than 12 months with external beam radiotherapy administered as adjuvant therapy. This excludes patients with T1 or stage I disease confined to the mucosa of the gallbladder. Their survival rates are extremely high and they are at very low risk for lymph node metastases.
- All patients with tumors beyond the mucosa are candidates for external beam radiotherapy. Patients with curative resection and AJCC stages T2-T4 who have had complete resection who receive radiation have a mean survival of over 16 months. This is compared to less than 6 months mean survival with surgery alone.
- 5-FU–based chemotherapy is usually given in conjunction with concurrent radiation therapy both in the adjuvant and palliative setting. No evidence-based clinical study exists to demonstrate the benefit of any form of adjuvant therapy in gallbladder cancer. Wherever possible, patients eligible for adjuvant therapy should be entered on a clinical trial. Gemcitabine by itself is an effective agent in the treatment of patients with unresectable recurrent or metastatic disease. The combination of gemcitabine and cisplatin15 or the combination of gemcitabine and capecitabine may be more effective than gemcitabine alone. This information is based on phase II clinical studies; because of the low numbers of patients with gallbladder cancer, there have been no definitive phase-III clinical trials to direct therapy for patients with this malignancy.
Patients with a good performance status should be considered for a clinical trial or with the regimens described in this section. Patients with a poor performance status may be best treated with supportive care.
Surgical Care
Complete surgical resection is the only therapy to offer a chance of cure in this disease. Unfortunately, only a minority of patients present with early-stage disease and are, therefore, considered for curative resection.
- Because of the high incidence of gallbladder cancer in a calcified (porcelain) gallbladder, patients with this finding should be strongly considered for an open cholecystectomy even if they are asymptomatic. It is best to avoid a laparoscopic cholecystectomy in this setting to avoid the risk of peritoneal seeding if, indeed, gallbladder cancer is present.
- Gallbladder cancer is sometimes an incidental pathology finding after a cholecystectomy is performed for reasons other than cancer. If the tumor is carcinoma in situ (Tis) or only invades the lamina propria (T1a) and the margins of resection are negative, then postoperative observation alone is acceptable. If the tumor is T1b or greater or the margins of resection are positive, then further surgical resection is necessary if no metastatic disease is present on evaluation (CT, MRI, chest radiograph). This additional surgery should include partial hepatic resection and regional lymphadenectomy (porta hepatis, gastrohepatic ligament, and retroduodenal lymph nodes). A bile duct resection may also be necessary depending on tumor size and location. If the original surgery was performed via a laparoscopic approach, then the port sites should also be resected to avoid tumor seeding.
- Patients who present with a gallbladder mass or jaundice are evaluated preoperatively for resectability as previously described. If the tumor is resectable, the patient undergoes a cholecystectomy with en bloc liver resection and regional lymphadenectomy. Bile duct excision may also be necessary (especially if jaundice is present). The operative morbidity and mortality rate increases with the complexity of the operative procedure.
- The surgical role in treatment of unresectable disease is usually limited to biopsy of the tumor for diagnosis and possible biliary decompression procedures.
Consultations
A radiation oncologist and medical oncologist should be part of the multidisciplinary team participating in the treatment of patients with gallbladder cancer.
Medication
Historically, chemotherapy has not shown significant activity in gallbladder carcinoma. Typically, 5-fluorouracil (5-FU) has been used with response rates of 10-24% in advanced disease. Often 5-FU is administered either as a bolus or as a prolonged infusion regimen with radiation. Capecitabine is a currently available oral alternative to a prolonged 5-FU infusion.
More recently, gemcitabine has shown activity in gallbladder cancer. Early phase studies show an increased response rate with gemcitabine combination therapy over historical treatment response rates with 5-FU alone. Gemcitabine has been studied in combination with cis-platinum and capecitabine.
Currently, no clearly defined standard exists for chemotherapy in gallbladder cancer. Patients should be encouraged to participate in clinical trials.
Antineoplastic agents
These agents inhibit cell growth and proliferation.
Gemcitabine (Gemzar)
Cytidine analog, after intracellular metabolism to active nucleotide, inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Cell cycle-specific for S phase.
This drug has been shown to have activity in a phase-2 trial against relapsed germ cell tumors.
Adult
1000 mg/m2 once weekly for as long as 7 wk or until toxic effects not tolerated; follow with 1 wk rest and subsequent cycles of once weekly infusion for 3 consecutive wk q4wk
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause myelosuppression (particularly thrombocytopenia); toxicities include flulike syndrome, LFT abnormality, maculopapular rash, pruritus, nausea, vomiting, dyspnea, hematuria, proteinuria, and hemolytic uremic syndrome; clearance reduced in women and elderly individuals
Cisplatin (Platinol)
Platinum-containing compound that exerts antineoplastic effect by covalently binding to DNA with preferential binding to N-7 position of guanine and adenosine. Can react with 2 different sites on DNA to cause cross-links. Platinum complex also can bind to nucleus and cytoplasmic protein. A bifunctional alkylating agent, once activated to aquated form in cell, binds to DNA, resulting in interstrand and intrastrand cross-linking and denaturation of double helix.
Modify dose on basis of CrCl. Avoid use if CrCl <60 mL/min.
Adult
20 mg/m2/d IV over 20-60 min for 5 d; repeat q21d for 4 cycles
Pediatric
Not established
Increases toxicity of bleomycin and ethacrynic acid
Documented hypersensitivity, pre-existing renal insufficiency, myelosuppression, and hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Administer adequate hydration before and 24 h after cisplatin dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea and vomiting, may occur
Capecitabine (Xeloda)
Prodrug of fluorouracil that undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. This step interferes with DNA, and to a lesser degree with RNA synthesis.
Adult
1250 mg/m2 PO q12h pc for 2 wk followed by 1 wk of rest period; administer as 3 wk cycle
Pediatric
Not established
Aluminum/magnesium hydroxide antacids or meals increase drug absorption; increased risk of bleeding with anticoagulants (monitor INR and PT frequently), NSAIDs, platelet inhibitors, thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents; coadministration with leucovorin may cause diarrhea, dehydration, and death from severe enterocolitis; may increase phenytoin levels
Documented hypersensitivity to drug or related products; severe renal impairment (CrCl <30 mL/min); dihydropyrimidine dihydrogenase (DPD) deficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adjust dose in moderate renal impairment (CrCl 30-50 mL/min); discontinue drug if intractable diarrhea, bone marrow suppression, myocardial ischemia, or stomatitis develop; caution in patients that have received extensive pelvic radiation or alkylating therapy; hand and foot syndrome characterized by numbness, dysesthesia/paresthesia, tingling, erythema, blistering, severe pain, desquamation, and painless or painful swelling may occur
More on Gallbladder Cancer |
| Overview: Gallbladder Cancer |
| Differential Diagnoses & Workup: Gallbladder Cancer |
 Treatment & Medication: Gallbladder Cancer |
| Follow-up: Gallbladder Cancer |
| References |
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Further Reading
Keywords
biliary cancer, biliary tract cancer, cancer of the biliary tree, gallbladder cancer, gallstones, cholesterol gallstones, chronic typhoid infections, abnormal pancreaticobiliary duct junctions, inflammatory bowel disease, IBD, polyposis coli, cholangiocarcinomas, primary sclerosing cholangitis, ulcerative colitis, liver flukes, chronic Salmonella typhi and paratyphi infections, and Helicobacter infection, Gardner syndrome, neurofibromatosis type I, hereditary nonpolyposis colon cancer, obesity, oral contraceptives, INH, isoniazid, methyldopa, chemical exposures, pesticides, rubber, vinyl chloride, occupational exposures, textile worker, petroleum worker, paper mill worker, shoemaker, water pollution, organopesticides, dichlorodiphenyltrichloroethane, benzene hexachloride, heavy metals, cadmium, chromium, lead, radiation exposure, radon in miners, apolipoprotein B gene, cytochrome P450 1A1 gene, CYP1A1, abdominal pain
