Ambrosy et al recently reported cardiotoxicity attributed to coronary spasm in 5 patients with cancer who underwent treatment with the 5-fluorouracil (5FU) prodrug capecitabine. All were subsequently rechallenged with capecitabine after commencement of calcium channel blockade (CCB) as an antivasospasm therapy. Because 4 of 5 patients experienced no recurrence of symptoms, the investigators concluded that this is a safe management approach in such patients. We believe that this conclusion is potentially dangerous and cannot currently be justified.

In contrast to the conclusions drawn from this small case series, a larger study of 58 patients who underwent 5FU chemotherapy found that high-dose CCB therapy did not reduce the incidence of cardiotoxicity compared to non-CCB-treated controls. This disparity aside, toxicity from 5FU-based agents has a spectrum of cardiac manifestations that include not only vasospasm-related ischemia but also nonischemic cardiomyopathy secondary to myocarditis. To therefore suggest antivasospasm therapy alone as an adequate prophylaxis method is misguided. Indeed, a recent report described a patient who developed an acute cardiomyopathy with severe left ventricular systolic dysfunction presenting with ventricular fibrillation arrest shortly after rechallenge with 5FU despite being commenced on CCB prophylaxis after the index presentation.

Rechallenge with 5FU-based therapy, with or without CCB prophylaxis, after presentation with cardiotoxicity cannot be safely recommended on the basis of this small case series, which is at odds with findings in larger studies and ignores the potentially catastrophic nonvasospastic cardiotoxic properties of these drugs. Conversion from 5FU-based therapy to raltitrexed, another thymidylate synthase inhibitor, currently appears to be a safe option in these patients.