What is the clinical evidence from this study?

Study design: Observational. Population: Patients hospitalized for cardiovascular events during fluoropyrimidine-based chemotherapy for cancer within the preceding 12 months (n=141). Intervention: Fluoropyrimidine reintroduction vs. Switch to alternative chemotherapy or palliative care. Primary outcome: Overall survival at 2-year follow-up (HR 1.77 for reintroduction vs alternative chemotherapy; HR 8.31 for reintroduction vs palliative care, 95% CI [0.92–3.42] vs alternative chemotherapy; [4.67–14.79] vs palliative care, p=0.088 vs alternative chemotherapy; <0.001 vs palliative care).

What question did this study set out to answer?

To assess the safety of reintroducing fluoropyrimidine chemotherapy in patients with a history of cardiotoxicity.

March 9, 2026Open Access

Fluoropyrimidine-induced cardiotoxicity: outcomes and safety of chemotherapy reintroduction in a retrospective cohort study

Q: What are the key findings of this study?

Fluoropyrimidine reintroduction resulted in a 14.8% recurrence of cardiotoxicity and tended to improve 2-year overall survival compared to switching chemotherapy (HR 1.77, p=0.088) and significantly compared to palliative care (HR 8.31, p<0.001) without increased hospitalizations.

Q: What question did this study set out to answer?

To assess the safety of reintroducing fluoropyrimidine chemotherapy in patients with a history of cardiotoxicity.

Key Result

Fluoropyrimidine reintroduction resulted in a 14.8% recurrence of cardiotoxicity and tended to improve 2-year overall survival compared to switching chemotherapy (HR 1.77, p=0.088) and significantly compared to palliative care (HR 8.31, p<0.001) without increased hospitalizations.

Key Points

To assess the safety of reintroducing fluoropyrimidine chemotherapy in patients with a history of cardiotoxicity.
Conducted a retrospective cohort study on patients with fluoropyrimidine-induced cardiotoxicity.
Implemented a multidisciplinary evaluation for candidate selection.
Applied cardiovascular management strategies and close monitoring during reintroduction.
Reintroduction of fluoropyrimidine demonstrated favorable outcomes for selected patients.
The benefit/risk balance was considered favorable under guided evaluations and management.

Study Design

Type

Observational (n=141)

Multicenter

Yes

Structured PICO

Does fluoropyrimidine reintroduction improve survival compared to alternative chemotherapy or palliative care in patients who experienced fluoropyrimidine-induced cardiotoxicity?

Population

141 patients who experienced a cardiovascular event during fluoropyrimidine-based chemotherapy for cancer within the preceding 12 months (follow-up cohort n=114). Median age 69, 68.1% male, France-based.

Intervention

Fluoropyrimidine reintroduction (n=54) guided by multidisciplinary evaluation, cardiovascular management, and close monitoring.

Comparator

Switch to a non-fluoropyrimidine alternative chemotherapy (n=25) or transition to palliative care (n=36).

Outcome

All-cause mortality and unplanned hospitalization over a 2-year follow-up period from the index cardiac event.hard clinical

Fluoropyrimidine reintroduction after cardiotoxicity appears feasible and may offer a survival benefit over alternative therapies when guided by multidisciplinary management, with an acceptable recurrence rate.

Main Result

Effect estimate: HR 1.77 for reintroduction vs alternative chemotherapy; HR 8.31 for reintroduction vs palliative care (95% CI [0.92–3.42] vs alternative chemotherapy; [4.67–14.79] vs palliative care)

Absolute Event Rate: 37.7% vs 64%

p-value: p=0.088 vs alternative chemotherapy; <0.001 vs palliative care

Limitations

Retrospective study design with potential selection and information bias
Conducted in two tertiary centers in France limiting generalizability
Small sample sizes in subgroups reducing statistical power
Survival analyses unadjusted for confounding variables such as age, comorbidities, tumor burden, and performance status
Heterogeneity in reintroduction protocols limiting reproducibility

Abstract

Our findings suggest that fluoropyrimidine reintroduction-guided by multidisciplinary evaluation, cardiovascular management, and close monitoring-appears to have a favorable benefit/risk balance for selected patients.

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Cite This Study

Rea et al. (Sun,) conducted a observational in Patients hospitalized for cardiovascular events during fluoropyrimidine-based chemotherapy for cancer within the preceding 12 months (n=141). Fluoropyrimidine reintroduction vs. Switch to alternative chemotherapy or palliative care was evaluated on Overall survival at 2-year follow-up (HR 1.77 for reintroduction vs alternative chemotherapy; HR 8.31 for reintroduction vs palliative care, 95% CI [0.92–3.42] vs alternative chemotherapy; [4.67–14.79] vs palliative care, p=0.088 vs alternative chemotherapy; <0.001 vs palliative care). Fluoropyrimidine reintroduction resulted in a 14.8% recurrence of cardiotoxicity and tended to improve 2-year overall survival compared to switching chemotherapy (HR 1.77, p=0.088) and significantly compared to palliative care (HR 8.31, p<0.001) without increased hospitalizations.

synapsesocial.com/papers/69af235f3eac3accde8a170b https://doi.org/https://doi.org/10.1007/s00520-026-10531-2

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