Risk Factors and Prevention of Cardiotoxicity Induced by 5-fluorouracil or Capecitabine

Cancer Chemother Pharmacol. 2006 Oct;58(4):487-93. doi: 10.1007/s00280-005-0178-1. Epub 2006 Jan 18.

Abstract

Aim: 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.

Method: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Atherosclerosis / complications*
  • Capecitabine
  • Comorbidity
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / adverse effects*
  • Fluorouracil / therapeutic use
  • Gastrointestinal Neoplasms / complications
  • Gastrointestinal Neoplasms / drug therapy*
  • Heart Diseases / chemically induced*
  • Heart Diseases / classification*
  • Heart Diseases / epidemiology
  • Heart Diseases / prevention & control
  • Humans
  • Kidney Diseases / complications
  • Kidney Diseases / metabolism
  • Male
  • Middle Aged
  • Nitroglycerin / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Vasodilator Agents / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Vasodilator Agents
  • Deoxycytidine
  • Capecitabine
  • Nitroglycerin
  • Fluorouracil