Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine.
OBJECTIVE
5-fluorouracil (5-FU) and its prodrug capecitabine are cardiotoxic. This retrospective study aimed to identify risk factors and to give practical measures to make such chemotherapy feasible if cardiotoxicity occur.


METHODS
Review of cardiotoxicity among 668 patients treated with 5-FU or capecitabine for gastrointestinal cancers.


RESULTS
Cardiotoxicity occurred in 29 cases (4.3%). The number of cases according to cardiotoxicity CTC grades 2-4 for patients with and without pre-existing cardiovascular disease were none, 10, and 2 cases, and 3, 14, and no cases, respectively (P=0.16). In three patients intercurrent decrease of renal clearances to <30, 48 and 71 ml min(-1) led to markedly increased cardiotoxicity. Chemotherapy dose reduction to 70 or 50%, either alone or in addition to antiangina medication prevented cardiotoxicity during subsequent chemotherapy in nine (60%) and three (20%) cases out of 15 assessable patients (P=0.001), respectively. To abolish symptoms of cardiotoxicity, sublingual nitroglycerine was efficient for 15 patients and inefficient for two (P=0.001).


CONCLUSIONS
Cardiac and renal co-morbidity are risk factors for 5-FU induced cardiotoxicity. In this situation, rechallenge with modified 5-FU-based chemotherapy regimen supported by symptomatic medical treatment is feasible.
Jensen
Søren Astrup
SA
Department of Oncology 5073, National University Hospital, 9 Blegdamsvej, 2100, Copenhagen, Denmark. soren.a.jensen@mail.tele.dk
Sørensen
Jens Benn
JB
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000150:complications*; D000069287:Capecitabine; D015897:Comorbidity; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000188:drug therapy*; D006331:Heart Diseases / Q000139:chemically induced* / Q000145:classification* / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D014665:Vasodilator Agents / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014665:Vasodilator Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005996:Nitroglycerin; D005472:Fluorouracil