Contemporary management and rechallenge practices for 5-fluorouracil-associated cardiotoxicity: an international cardio-oncology society survey

Background

5-fluorouracil (5-FU)–associated coronary vasospasm is a clinically important cardiotoxicity often leading to cancer therapy interruption, yet evidence guiding acute management and safe rechallenge is limited. We surveyed International Cardio-Oncology Society (ICOS) members to define contemporary practice patterns, variability in care, and barriers to rechallenge.

Methods

An electronic survey was distributed to ICOS members. Of 152 responses, 133 were analyzed after exclusions; item-level denominators had variable completion. Practices were summarized, compared by practice type and years of cardio-oncology experience, using chi-square/Fisher’s exact tests (two-sided p<0.05).

Results

Most respondents practiced at academic centers (59.1%, 78/132) and had <5 (36.4%, 48/132), 5–10 (38.6%, 51/132), or >10 years (25.0%, 33/132) of cardio-oncology experience. In response to 5-FU treatment, chest pain (91.0%, 121/133), ST-segment changes (54.9%, 73/133), and troponin elevation (40.6%, 54/133) were commonly observed. Symptom onset was <24 h (25.2%, 33/131), 1–3 d (44.3%, 58/131), >3 d (5.3%, 7/131), or variable (25.2%,33/131). Mortality attributable to 5-FU cardiotoxicity was reported by 23.3% (31/133).

Initial work up included electrocardiography (93.2%, 123/132), troponin measurement (87.1%, 115/132), and echocardiography (79.5%, 105/132). Urgent coronary angiography was pursued in 35.6% (47/132) of cases and routinely in 84.1% (111/132). Acute management strategies varied, including 5-FU discontinuation (76.5%, 101/132), nitrates (69.7%, 92/132) or calcium channel blockers (59.8%, 79/132), and telemetry (50.0%, 66/132) or ICU-level care (26.5%, 35/132).

ICOS respondents were involved in rechallenge decisions in 70.0% (91/130) and 93.8% (122/130) co-managed with oncology. Strategies included vasodilator pre-treatment (74.2%, 92/124), dose reduction (45.2%, 56/124), bolus-only dosing (33.1%, 41/124), and switch to capecitabine (29.8%, 37/124). 91.2% (103/113) reported success in ≥50% of rechallenge cases. Institutional protocols were reported as present (18.3%, 23/126) or in development (22.2%, 28/126); 24.4% (30/123) reported lack of clear guidelines as a practice barrier to rechallenge. Academic ICOS respondents more often reported always/frequently communicating directly with oncology (97.4% vs 86.8%; p=0.03). More years in cardio-oncology practice was associated with rechallenge involvement (p<0.01, and guideline gaps were reported as an impediment to rechallenge (p<0.01).

Conclusion

In a survey of ICOS members, management and rechallenge practices for suspected 5-FU–cardiotoxicity varied substantially. Rechallenge was commonly attempted with vasodilator prophylaxis and monitored re-exposure, yet formal protocols are uncommon, and guideline gaps persist. Our study underscores the need for consensus recommendations and prospective studies to inform risk stratification and safer 5-FU rechallenge strategies.