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Objective <p>Breast cancer remains a major cause of morbidity and mortality among Ugandan women, who often present at younger age with advanced disease. Doxorubicin is central to treatment regimens, but current dosing is adapted without validation in this setting. We conducted the first pilot prospective pharmacokinetic study among 21 breast cancer women at Uganda Cancer Institute.</p> Results <p>Participants received doxorubicin (60&#xa0;mg/m²) intravenously over 30&#xa0;min. Samples were collected at pre-infusion, 4- and 24-hours post-infusion. Plasma concentrations were quantified using HPLC-UV and non-compartmental PK analysis was performed in R (Xgxr-v1.1.4). The mean age was 45 ± 12 years and 81% presented with metastatic disease. At 4&#xa0;h, mean plasma concentration was 15.45 ± 10.97 ng/mL (CV: 71%; 95% CI: 10.46–20.44), declining to 6.58 ± 4.17 ng/mL (CV: 63%; 95% CI: 4.68–8.48) at 24&#xa0;h. The mean AUC<sub>0–24</sub> was 251.16 ± 151.14 ngh/mL (CV: 60%; 95% CI: 182.36–319.96). Our study suggests lower early systemic exposure, potentially reducing therapeutic efficacy. The high prevalence of advanced-stage disease underscores diagnostic delays and poor prognosis. These preliminary findings warrant larger PK studies integrating genetics and clinical outcomes to validate and extend our hypothesis-generating observations to guide treatment in this setting.</p>

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Subtherapeutic exposure in doxorubicin pharmacokinetics among Ugandan breast cancer patients: a pilot study with implications for personalized therapy

  • 期刊论文

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  • 发表日期：

    2026年3月20日

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  • Dave Darshit,
  • Osinde Godfrey,
  • Christine Sekaggya-Wiltshire,
  • Mukonzo Jackson,
  • Ronald Kadada Karyaburo,
  • Allan Buzibye,
  • Denis Omali,
  • Nixon Niyonzima,
  • Sanjanaa Srikant,
  • Dhara Dave

摘要

Objective

Breast cancer remains a major cause of morbidity and mortality among Ugandan women, who often present at younger age with advanced disease. Doxorubicin is central to treatment regimens, but current dosing is adapted without validation in this setting. We conducted the first pilot prospective pharmacokinetic study among 21 breast cancer women at Uganda Cancer Institute.

Results

Participants received doxorubicin (60 mg/m²) intravenously over 30 min. Samples were collected at pre-infusion, 4- and 24-hours post-infusion. Plasma concentrations were quantified using HPLC-UV and non-compartmental PK analysis was performed in R (Xgxr-v1.1.4). The mean age was 45 ± 12 years and 81% presented with metastatic disease. At 4 h, mean plasma concentration was 15.45 ± 10.97 ng/mL (CV: 71%; 95% CI: 10.46–20.44), declining to 6.58 ± 4.17 ng/mL (CV: 63%; 95% CI: 4.68–8.48) at 24 h. The mean AUC0–24 was 251.16 ± 151.14 ngh/mL (CV: 60%; 95% CI: 182.36–319.96). Our study suggests lower early systemic exposure, potentially reducing therapeutic efficacy. The high prevalence of advanced-stage disease underscores diagnostic delays and poor prognosis. These preliminary findings warrant larger PK studies integrating genetics and clinical outcomes to validate and extend our hypothesis-generating observations to guide treatment in this setting.