Cancer Chemotherapy and Pharmacology

, Volume 82, Issue 5, pp 887–898 | Cite as

Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood

  • Z. LiuEmail author
  • J. Martin
  • L. Orme
  • B. Seddon
  • J. Desai
  • W. Nicholls
  • D. Thomson
  • D. Porter
  • G. McCowage
  • C. Underhill
  • N. Cranswick
  • M. Michael
  • M. Zacharin
  • A. Herschtal
  • J. Sivasuthan
  • D. M. Thomas
Original Article



For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap.

Patients and methods

A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics.


The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1–3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI − 0.005 to − 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09–1.4).


Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.


Doxorubicin Doxorubicinol Pharmacokinetics modelling Adolescent and young adult Gender Hodgkin’s lymphoma Ewing sarcoma Osteosarcoma 



Funding was provided by Victorian Cancer Agency (Grant no. CTPS_08_18).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Z. Liu
    • 1
    • 2
    Email author
  • J. Martin
    • 1
  • L. Orme
    • 3
    • 4
  • B. Seddon
    • 5
  • J. Desai
    • 3
  • W. Nicholls
    • 6
    • 7
  • D. Thomson
    • 7
  • D. Porter
    • 8
  • G. McCowage
    • 9
  • C. Underhill
    • 10
  • N. Cranswick
    • 2
  • M. Michael
    • 3
  • M. Zacharin
    • 2
  • A. Herschtal
    • 3
  • J. Sivasuthan
    • 3
  • D. M. Thomas
    • 11
  1. 1.School of Medicine and Public HealthUniversity of NewcastleCallaghanAustralia
  2. 2.Clinical Pharmacology and Department of MedicineThe Royal Children’s HospitalMelbourneAustralia
  3. 3.Division of Cancer Medicine, Peter MacCallum Cancer CentreUniversity of MelbourneMelbourneAustralia
  4. 4.Royal Children’s HospitalBrisbaneAustralia
  5. 5.University College London HospitalLondonUK
  6. 6.Brisbane Children’s HospitalBrisbaneAustralia
  7. 7.Princess Alexandra HospitalBrisbaneAustralia
  8. 8.Starship Children’s HospitalAucklandNew Zealand
  9. 9.Children’s Hospital WestmeadSydneyAustralia
  10. 10.Border Medical OncologyAlbury-WodongaAustralia
  11. 11.Cancer DivisionGarvan Institute of Medical ResearchDarlinghurstAustralia

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