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Anthracycline total exposure calculator

NOTE: There is lack of consensus on the most accurate conversion between anthracyclines in predicting cardiac toxicity. This tool is based on best available literature review. Recent ESC guidelines have recommended conversion ratios from studies of pediatric cancer survivors in adult patients (12). See further details below.

Patient type:
Adult ≥18 years.
The adult model is based on manufacturer's guidelines detailed in summaries of product characteristics (SPC) and package inserts.
Pediatric < 18 years
Includes:
1)Feijen et al
2)Children's Oncology Group (COG) models

Enter the total cumulative dose of each anthracycline received.







Model:
Feijen et al
COG Children's Oncology Group

Enter the total cumulative dose of each anthracycline received.








Enter the total cumulative dose of each anthracycline received.







Total anthracycline exposure:

Anthracycline equivalent exposure conversion calculator for cardiac toxicity

  • There is a lack of consensus on the most accurate conversion ratio between different classes of anthracyclines in predicting cardiac-toxicity. The conversions provided here are based on best available literature review and manufacturer guidance.

  • This tool calculates total anthracycline exposure by adding the equivalent dose of each anthracycline according to the conversion model selected.

  • The result is displayed as mg/m2 of doxorubicin equivalent and the equivalent exposure in terms of other anthracycline drugs is also displayed in smaller font.

  • Many factors influence development of anthracycline related cardiac dysfunction. This includes pre-existing cardiac disease, cardiovascular risk factors, concomitant mediastinal radiotherapy and genetic predisposition(1).

  • Risk of cardiac toxicity increases with cumulative anthracycline dosage.

  • Cardiac toxicity can occur at exposures well below maximum doses.

  • Regular echocardiography is critical in the early detection of cardiac dysfunction.

  • See also the HFA-ICOS Cardiovascular Risk Assessment Tool for baseline risk stratification of patients prior to anthracycline therapy.

Adult patient anthracycline dose conversion

  • Conversion ratios for adult patients in this calculator are based on the manufacturer’s guidance on maximum lifetime dose of each anthracycline detailed in the summaries of product characteristics (SPC) (2-6), package inserts (7-10) and published management guidelines (11).

  • We note however that some recent guidelines have extrapolated studies performed in pediatriac patients and applied these in adult guidelines(12).

  • Therefore individual clinician judgement is required when converting between different classes of anythracyclines.

  • The conversion ratios used in the adult model are listed below.

  • It is recommended not to exceed the maximum equivalent cumulative lifetime doses of anthracycline listed in the table below.

Drug Maximum cumulative lifetime dose (mg/m2) Conversion factor for mg/m2 doxorubicin equivalent
Doxorubicin 550 1
Epirubicin 900 0.611
Daunorubicin 550 1
Idarubicin 150 3.667
Mitoxantrone 140 3.929

Pediatric patient anthracycline dose conversion

  • We have provided conversion ratios based on two models.

  • The Feijen model is based on a multicenter cohort study of 20532 childhood cancer survivors who survived 5 or more years (13). An agent-specific cardiomyopathy equivalence ratio (relative to doxorubicin) was estimated for each dose category as a ratio of the hazard ratios, and then a weighted mean determined the overall agent-specific equivalence ratio across all dose categories.

  • Note that the Feijen model does not provide a conversion ratio for idarubicin due to insufficient numbers.

  • The conversion ratios used in the Feijen model are as follows:
Drug Conversion factor for mg/m2 doxorubicin equivalent
Doxorubicin 1
Epirubicin 0.8
Daunorubicin 0.6
Mitoxantrone 10.5

  • The COG model is based on guidelines provided by the Children’s Oncology Group(14-16).
  • The conversion ratios used in the COG model are as follows:

Drug Conversion factor for mg/m2 doxorubicin equivalent
Doxorubicin 1
Epirubicin 0.67
Daunorubicin 0.5
Idarubicin 5
Mitoxantrone 4

References:
  1. Henriksen PA. Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart. 2018;104(12):971-977. doi:10.1136/heartjnl-2017-312103
  2. https://www.medicines.org.uk/emc/product/6112/smpc
  3. https://www.medicines.org.uk/emc/product/6361/smpc
  4. https://www.medicines.org.uk/emc/product/4004/smpc
  5. https://www.medicines.org.uk/emc/product/776/smpc
  6. https://www.medicines.org.uk/emc/product/3678/smpc
  7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf
  8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf
  9. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf
  10. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050661s014lbl.pdf
  11. Blake L., Anthracycline-Induced Cardiotoxicity in Adults. JHOP. 2018. Vol 8, No 4
  12. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244
  13. Feijen EAM, Leisenring WM, Stratton KL, et al. Derivation of Anthracycline and Anthraquinone Equivalence Ratios to Doxorubicin for Late-Onset Cardiotoxicity. JAMA Oncol. 2019;5(6):864-871. doi:10.1001/jamaoncol.2018.6634
  14. Andolina JR, Dilley K. Anthracycline-induced cardiac toxicity more likely in underweight childhood cancer survivors. J Pediatr Hematol Oncol. 2010;32(5):411-415. doi:10.1097/MPH.0b013e3181dccd37
  15. Armenian SH, Hudson MM, Mulder RL, et al. Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. 2015;16(3):e123-36. doi:10.1016/S1470-2045(14)70409-7
  16. Available at: http://www.survivorshipguidelines.org/ COG: Long term follow-up guidelines.