Severe toxicity of capecitabine following uncomplicated treatment with 5-fluorouracil/leucovorin

Abstract

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 58 year old woman with metastatic rectal carcinoma who developed severe gastrointestinal toxicity when the thus far well-tolerated intravenous 5-fluorouracil (5-FU)/leucovorin containing chemotherapeutic regimen was replaced by the same chemotherapeutic regimen in combination with the oral 5-FU prodrug capecitabine. This increased toxicity is probably due to the intracellular retention of polyglutamated folates induced by prior leucovorin therapy which, upon subsequent administration of capecitabine, will result in an enhanced and prolonged inhibition of the, for DNA synthesis important, enzyme thymidylate synthase, essentially creating a situation equivalent to overdosing.