title: Use of raltitrexed as an alternative to 5-fluorouracil and capecitabine in cancer patients with cardiac history.
abstract: OBJECTIVE
  Fluoropyrimidines are the backbone of the majority of approved chemotherapy regimens for colorectal cancer (CRC). However, there are reports of fluoropyrimidine treatments being associated with cardiotoxicity which have led to permanent cardiovascular damage and even death. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-fluorouracil (5-FU) is not tolerated or inappropriate. A systematic review was undertaken to determine the incidence of cardiotoxicity associated with 5-FU, capecitabine and raltitrexed.
  
  
  METHODS
  An electronic search of PubMed was undertaken to identify articles relating to cardiotoxicity associated with 5-FU, capecitabine or raltitrexed, published between January 1991 and August 2011. Additionally, a retrospective review of cardiotoxicity associated with raltitrexed at our treatment centres was conducted.
  
  
  RESULTS
  Twenty studies were examined. The overall incidence of cardiotoxicity associated with 5-FU/capecitabine varied between 0.55% and 19% (mean: 5.0%, median: 3.85%). No published data were identified reporting cardiotoxicity associated with raltitrexed. A retrospective review at our treatment centres revealed that the incidence was 4.5% amongst high-risk patients treated with raltitrexed (n=111) for advanced gastrointestinal cancer with a significant cardiac history and/or previous cardiotoxicity with 5-FU or capecitabine.
  
  
  CONCLUSIONS
  The incidence of cardiotoxicity associated with raltitrexed in patients with advanced CRC treated is favourable in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with other fluoropyrimidines or were unable to tolerate capecitabine due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or significant cardiovascular risk factors.
authors.affiliation: Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Kelly
authors.forename: Neel
authors.initials: N
authors.lastname: Bhuva
authors.forename: Mark
authors.initials: M
authors.lastname: Harrison
authors.forename: Andrew
authors.initials: A
authors.lastname: Buckley
authors.forename: Mark
authors.initials: M
authors.lastname: Saunders
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006331:Heart Diseases / Q000139:chemically induced / Q000150:complications; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; D003841:Deoxycytidine; D000069287:Capecitabine; C068874:raltitrexed; D005472:Fluorouracil