Cardiotoxicity with trabectedin in the treatment of advanced soft tissue sarcoma

Trabectedin is used routinely in the palliative management of patients with advanced soft tissue sarcoma. It is not generally considered to be cardiotoxic, and there is no specific caution for its use in patients with a history of cardiac disease or risk factors. Here, we report six cases from a single academic centre where life-threatening cardiotoxicity occurred acutely during treatment with trabectedin. These patients had a median age of 72.5 years (range: 68–81) at presentation with cardiotoxicity, significantly higher than the median ages of patients treated with trabectedin in clinical trials. Cardiotoxicity occurred between cycle 1, day 10, and cycle 5, day 5 of treatment (with three events occurring during cycle 2, and one during cycle 3). Two patients had a previous cardiac history and three patients had other relevant cardiac risk factors. Five patients had been treated previously with anthracyclines. Two patients developed acute pulmonary oedema, two developed fast atrial fibrillation, one developed an ST-elevation myocardial infarction and one suffered a fatal cardiac arrest. Two had unequivocal evidence of myocardial ischaemia, and two events were acutely fatal. Trabectedin was immediately discontinued in all cases and, for the four nonfatal events, there were no recurrences of the cardiac events. As no other definitive precipitants were identified, we consider these events to be related to trabectedin toxicity. We therefore urge caution with the use of trabectedin in elderly patients, and those with a previous cardiac history, abnormal cardiac function or significant cardiac risk factors including pericardiac lesions (present in two cases reported here). Correspondence to Gary J. Doherty, MB BChir, PhD, MRCP, Department of Oncology, Addenbrooke's Hospital, Box 193, Cambridge CB2 0QQ, UK Tel: +44 122 358 6705; fax: +44 122 321 7094; e-mail: gd231@cam.ac.uk Received June 28, 2018 Accepted August 15, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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