title: 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.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. f.schneiders@vumc.nl
authors.forename: Famke L
authors.initials: FL
authors.lastname: Schneiders
authors.forename: H Pieter
authors.initials: HP
authors.lastname: van den Berg
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.forename: Hans J
authors.initials: HJ
authors.lastname: van der Vliet
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069059:Atorvastatin; D017298:Bisoprolol / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D000069287:Capecitabine; D003085:Colic / Q000139:chemically induced; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D045823:Ileus / Q000139:chemically induced*; D002955:Leucovorin / Q000627:therapeutic use; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011758:Pyrroles / Q000627:therapeutic use; D018879:Ventricular Premature Complexes / Q000150:complications / Q000188:drug therapy; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000964:Antimetabolites, Antineoplastic; D006538:Heptanoic Acids; D011758:Pyrroles; D003841:Deoxycytidine; D000069287:Capecitabine; D000069059:Atorvastatin; D002955:Leucovorin; D005472:Fluorouracil; D017298:Bisoprolol