# Caution: cumulative anthracycline dose and the heart

Source: https://onco.cc/pairings/doxorubicin-cardio-caution/  
OnCo record `doxorubicin-cardio-caution` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Every dose of doxorubicin adds to a lifetime total; above roughly 450 mg/m2 heart failure risk rises steeply, so sarcoma and lymphoma regimens are capped and hearts are monitored.

## Summary

Every dose of doxorubicin adds to a lifetime cumulative total, and this caution pairing links the anthracycline with cardio-oncology because the risk of heart failure rises steeply above roughly 450 mg/m2. The mechanism is topoisomerase II beta-mediated damage to cardiomyocytes that is dose-dependent and irreversible, and the risk is higher with chest radiotherapy, trastuzumab and at the extremes of age. Decades of cohort data and randomised trials of dexrazoxane support the warning, and mitigation includes dexrazoxane, liposomal doxorubicin, continuous infusion and echocardiographic surveillance. The caution applies in sarcoma, Hodgkin lymphoma, diffuse large B-cell lymphoma and triple-negative breast cancer, where regimens are capped and hearts are monitored.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Doxorubicin + Cardio-oncology
- Type: caution
- Rationale: Topoisomerase IIβ-mediated cardiomyocyte damage is dose-dependent and irreversible.
- Evidence: Decades of cohort data; dexrazoxane RCTs.

## Sources

- Swain et al., Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials (Cancer 2003): https://doi.org/10.1002/cncr.11407

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/)
- drugs: [Doxorubicin](https://onco.cc/drugs/doxorubicin/)
- key papers: [Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials](https://onco.cc/key-papers/paper-swain-cancer/)

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