519O - Final results of Australasian Gastro-Intestinal Trials Group (AGITG) ARCTIC study: an international audit of raltitrexed for patients with cardiac t...

Date 01 October 2012
Event ESMO Congress 2012
Session Gastrointestinal tumors, colorectal
Topics Complications/Toxicities of treatment
Colon and Rectal Cancer
Presenter Timothy Price
Authors T.J. Price1, K. Wilson2, R.J. Simes2, D. Yip3, C.S. Karapetis4, N. Tebbutt5, V. Gebski2, M. Fournier2, D. Ferry6, D. Ransom7
  • 1The Queen Elizabeth Hospital, 5012 - Woodville South/AU
  • 2Ctc, University of Sydney, Sydney/AU
  • 3Medical Oncology, The Canberra Hospital, Canberra/AU
  • 4Department Of Medical Oncology, Flinders Medical Center, AU-5042 - Bedford Park/AU
  • 5Austin Health, University of Melbourne, Melbourne/AU
  • 6Medical Oncology, Russells Hall Hospital, Dudley/UK
  • 7Medical Oncology, Royal Perth Hospital, Perth/AU




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%*. Management of these patients remains poorly defined and options include continuing same dose/schedule of FP, adding a nitrate and calcium antagonist, switching administration schedule of FP, or substituting with raltitrexed, the later based primarily on case reports.


AGITG and 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.


42 patients were included in this clinical audit. Cancer diagnoses included colorectal (39pts), oesophageal (2) and ampullary carcinoma (1). Median age - 62 years (range 36-81). 27 patients (64%) were male. Median number of cycles prior to switching to raltitrexed was 2 (range 1-11). FP regimens included FOLFOX, CAPOX, continuous infusion 5FU, ECF, capecitabine alone. 40 patients had angina, 5 MI, and 2 arrhythmia with some patients experiencing >1 event at that time. 8 patients experienced two separate CT events, and 2 had 3 events prior to switching to raltitrexed. Following CT, 9 patients received raltitrexed alone, 32 received raltitrexed in combination with other agents or radiotherapy and one received raltitrexed alone followed by combination. Median number of raltitrexed cycles was 6 (range 1-21). One patient (CT rate 2.4%, 95% CI: 0.1-12.3) experienced a potentially related cardiac event (acute arrhythmia 5 mths into therapy) after switching to raltitrexed, a CT rate significantly lower than the 20% reported when continuing FP (exact binomial test p = 0.004).


The rate of recurrent CT after switching from FP to raltitrexed was low. The strategy of switching to raltitrexed may represent an acceptable option for patients that are deriving a benefit from FP based chemotherapy but in whom cardiac toxicity is a concern. (* Jensen SA et al. Cancer Chemotherapy & Pharm. 58:487-93, 2006).


D. Ransom: Unrestricted research grant from Astra Zeneca.

All other authors have declared no conflicts of interest.