P-0255 Use of Raltitrexed as an Alternative to 5-Fu and Capecitabine in Cancer Patients with Cardiac History

Abstract

ABSTRACT Introduction 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. A review of 20 studies suggests an overall mean incidence of 5-fluorouracil (5-FU) associated cardiotoxicity of 4.99%. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-FU is not tolerated or inappropriate. This study aimed to determine the incidence of raltitrexed-associated cardiotoxicity at our treatment centres. Methods We conducted a retrospective review of 111 patients treated with raltitrexed for primary gastrointestinal tumours at two UK treatment centres. The time period for inclusion was January 2008–January 2011 inclusive at the Christie Hospital, Manchester, UK, and April 2006–March 2011 inclusive at Mount Vernon Cancer Centre, Middlesex, UK. This consisted of a pharmacy database search for patients having received raltitrexed. Electronic patient records and patient notes were accessed for each patient and the following data were collected: treatment intent, reason for raltitrexed administration (first-line due to cardiac comorbidity or following 5-FU complications), number of cycles of raltitrexed received, complications whilst on raltitrexed treatment, and patient outcome. Results A total of 111 patients with advanced CRC treated with raltitrexed in two treatment centres were included in the retrospective review. Patients were aged 33–85 years (median age: 68 years) and 74% were male (male: n=82; female: n=29). In this audit, 41.4% (n=46) of patients received first-line raltitrexed treatment whilst 58.5% (n=65) of patients switched to raltitrexed from another regimen; 96.9% (n=63) of these patients receiving second-line raltitrexed therapy switched following cardiovascular complications associated with capecitabine. Of the patients receiving first-line raltitrexed therapy, 89% had a history of ischaemic heart disease and 4.3% had a history of cerebrovascular accident or transient ischaemic attack. The reasons for receiving first-line raltitrexed therapy were not documented in three patients. The study revealed that five of the 111 patients had confirmed cardiac complications whilst receiving raltitrexed therapy, equating to an incidence of 4.5%. This is in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with capecitabine (n=3) or were considered unable to tolerate capecitabine due to their previous cardiac history (n=2) and hence represents a favourable result. Of these, two patients experienced acute coronary syndrome, one suffered from myocardial infarction, one had chest pain and one suffered from a stroke. Conclusion The incidence of cardiotoxicity associated with raltitrexed in patients with advanced CRC is favourable in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with fluoropyrimidines or were unable to tolerate fluoropyrimidines due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or with significant cardiovascular risk factors.