Results of Australasian Gastrointestinal Trials Group (AGITG) Arctic study: An international audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines (FP).

Abstract

e13007 Background: Cardiac toxicity (CT) is an uncommon but potentially fatal side effect of FP. The incidence of further CT if the same chemotherapy is continued is reported to be 20% (Jensen SA et al. Risk factors and prevention of cardiac toxicity induced by 5-fluorouracil or capecitabine. Cancer Chemotherapy & Pharm. 58:487-93, 2006). Management of these patients remains poorly defined. Treatment options include continuing same dose and schedule of FP, adding a nitrate and calcium antagonist; switching to bolus FP; or substituting with raltitrexed. Previous publications of patients experiencing CT and switching FP to raltitrexed are limited to case reports. Methods: AGITG & OCTO (Oncology Clinical Trials Office – Oxford) members identified patients who had CT from FP, and were subsequently switched to raltitrexed. CT included angina, myocardial infarct (MI) or arrhythmia. A coronary angiogram was not mandatory. Results: 38 patients were included in clinical audit. Cancer diagnoses included colorectal (35pts), cervix (1), oesophageal (1) and ampullary carcinoma (1). Median age - 61 years (range 36-81). 24 patients (63%) were male. Median number of cycles prior to switching to raltitrexed was 2 (range 1-11). FP regimens included FOLFOX, CAPOX, continuous infusion 5FU, capecitabine alone. 35 patients had angina, 6 MI, and 1 arrhythmia with some patients experiencing >1 event at that time. 7 patients experienced two separate CT events, and 2 had three events prior to switching to raltitrexed. Following CT 8 patients received raltitrexed alone, 29 received raltitrexed in combination with other agents or radiotherapy and one received raltitrexed alone followed by combination. Median number of raltitrexed cycles was 5 (range 1-21). After switching to raltitrexed 2 patients experienced another cardiac event (5.3%, 95% CI:1.5-17.3), significantly different from 20% (p=0.023), the reported rate of cardiac toxicity due to continuing FP. Conclusions: For patients who experience CT from FP switching to raltitrexed is an option with the rate of additional cardiac events lower than previously reported for continuing same FP.