Treatment of the jaundiced patient with breast carcinoma

BACKGROUND: Breast carcinoma in the setting of liver metastases and jaundice raises a complex therapeutic dilemma. Not only is the prognosis poor but toxicity related to treatment can be unpredictable due to altered drug clearance. Guidelines built around dose reduction have been suggested but often do not address the varied presentations in clinical medicine. Bilirubin exceeding 5.0 mg% often is considered an absolute contraindication to the administration of chemotherapeutic agents dependent on hepatic metabolism. METHODS: A 55-year-old woman with metastatic breast carcinoma to the liver and hyperbilirubinemia was treated with sequential, empiric chemotherapy agents with the goal of preventing severe toxicity through dose reduction, avoidance of combination therapy, divided doses (weekly therapy), and selection of drugs less dependent on hepatic clearance. Several attempts did not yield a regimen with a successful response, but toxicity was minimal. Eventually, a successful schedule and dose of an agent cleared by liver metabolism was individualized for the patient. RESULTS: After eight cycles of low dose weekly doxorubicin chemotherapy, the patient's symptoms resolved, bilirubin level normalized, and performance status returned to baseline. The patient remained on treatment and was alive 12 months later. CONCLUSIONS: The authors propose that altering a drug schedule by dividing doses may minimize toxicity, maintain dose intensity, and represent an alternative strategy for the treatment of patients with hepatic impairment.