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4CPS-100 Anthracycline dosing in obese adult patients: a systematic review
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  1. B Tapia,
  2. A Casas,
  3. B Torroba,
  4. C Fraile,
  5. A Gutierrez,
  6. B Fernandez,
  7. M Serrano-Alonso,
  8. MA García Del Barrio
  1. Clinica Universidad De Navarra, Hospital Pharmacy, Pamplona, Spain

Abstract

Background and importance Chemotherapy dosing for obese patients (body mass index (BMI) ≥30 kg/m2) remains undefined. Most recent publications discourage arbitrary dose reductions that can compromise efficacy. However, because of the dose dependent cardiotoxicity of anthracyclines and also the inherent obesity related cardiovascular risk factors, it is advisable to review the evidence available on toxicity in this population.

Aim and objectives To define the most adequate dose strategy for anthracyclines in obese adult patients based on efficacy and toxicity results and/or pharmacokinetic data.

Material and methods We conducted a systematic review in Pubmed, Scopus and Web of Science using predefined keywords ((obese or obesity) and (daunorubicin or doxorubicin or epirubicin or idarubicin)). We excluded paediatric and non-English papers. Moreover, we looked at studies with relevant information about safety and efficacy.

Results Ten articles on doxorubicin, 4 on epirubicin, 2 on idarubicin and 1 on daunorubicin were included. Doxorubicin pharmacokinetics was evaluated in two articles: clearance was reduced and area under the curve was increased in obese patients but there were no statistically significant differences (SSD). Regarding efficacy, obese patients had better response ratios with no dose reduction with daunorubicin and idarubicin, but the difference was not significant. Epirubicin showed a better response when the full dose was used in neoadjuvant chemotherapy but there was no difference in progression free (PFS) or overall (OS) survival. One article reported worse pathological complete response, PFS and OS when the dose was reduced in obese breast cancer patients. Another article did not show SSD in recurrence risk and mortality when using a full dose, except if BMI ≥35 kg/m² when mortality was higher (p<0.05). Two articles found worse PFS in obese versus non-obese patients when receiving the full dose. Regarding safety, we found three articles that showed more toxicity but without SSD. One meta-analysis reported an increase in cardiovascular risk with increasing BMI but could not establish if it was due to the use of full doses or obesity itself.

Conclusion and relevance The literature regarding safety and efficacy is not consistent. As there are better responses with full dose anthracyclines and toxicity can be monitored, dose reduction in obese patients is not recommended. However, the presence of other comorbidities may be a reason for dose reduction.

References and/or acknowledgements No conflict of interest.

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