The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm

• Published in: PloS one 2022-04, Vol.17 (4), p.e0265767-e0265767
• Main Authors: Zafar, Amna, Drobni, Zsofia D, Lei, Matthew, Gongora, Carlos A, Quinaglia, Thiago, Lou, Uvette Y, Mosarla, Ramya, Murphy, Sean P, Jones-O'Connor, Maeve, Mahmood, Ali, Hartmann, Sarah, Gilman, Hannah K, Weekes, Colin D, Nipp, Ryan, Clark, John R, Clark, Jeffrey W, Blaszkowsky, Lawrence S, Tavares, Erica, Neilan, Tomas G
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Biology and Life Sciences; Calcium channel blockers; Calcium Channel Blockers - therapeutic use; Calcium channels; Cardiology; Cardiotoxicity; Cardiovascular disease; Care and treatment; Chemotherapy; Colorectal cancer; Complications and side effects; Coronary heart disease; Coronary Vasospasm - chemically induced; Coronary Vasospasm - drug therapy; Coronary vessels; Drug dosages; Fluorouracil; Fluorouracil - adverse effects; Gastrointestinal cancer; Heart; Hematology; Hospitals; Humans; Medical schools; Medicine; Medicine and Health Sciences; Myocardial infarction; Neoplasms - drug therapy; Nitrates; Nitrates - therapeutic use; Oncology; Pain; Patient outcomes; Patients; Physical Sciences; Pretreatment; Retrospective Studies; Safety; Survival; Variables; Vasoconstriction
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0265767

Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.