Liver insufficiency due to breast cancer metastasesFast biological response with capecitabine

Abstract

Capecitabine, an oral fluoropyrimidine that mimics continuous infusion 5-fluorouracil (5-FU), is now recognized as a standard treatment after failure of anthracycline and taxane therapy in metastatic breast cancer (1). About 40% of these women have liver metastases and some of them develop liver insufficiency. This particular situation is quickly fatal in almost every case. Here, we report a patient with liver insufficiency due to breast cancer metastases who dramatically improved with capecitabine. This hormone-refractory 70-year-old woman was first treated with an epirubicincontaining regimen for bone metastases. Six months later, she received weekly paclitaxel for liver metastases. A partial remission was obtained but she relapsed only 3 months after the end of taxane therapy. At this time, she presented with jaundice caused by a massive metastatic liver infiltration as demonstrated by magnetic resonance imaging. Liver enzymes were all profoundly disturbed (see Table) and CA 15.3 was highly elevated (6380 U/ml, nl B/25). Capecitabine was started at a standard dose of 1250 mg/m 2 , twice daily, and we observed a dramatic biological response in only 10 days. At day 30, total bilirubin remained slightly elevated at 2.4 mg/ dl (nl B/1.2) but became normal at day 60. Liver magnetic resonance performed two months after the start of capecitabine showed a partial remission according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. No adverse events were reported except mild anemia. This illustrates that capecitabine, although given with caution to patients with impaired hepatic function (2), may be useful when liver insufficiency appears due to metastases. A few drugs only are available in this situation. Continuous 5-FU can be given, but only small phase II trials have studied its efficacy after anthracycline and taxane treatment in metastatic breast cancer (3, 4). Here, we were impressed by the fast biological and clinical improvement. This might be explained by the activity of the enzyme thymidine phosphorylase, which mediates the final transformation step from capecitabine to 5FU. This enzyme has a higher activity in tumor tissue than in normal tissue (5), thus increasing the specificity of conversion to 5-FU in malignant cells (6).