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

乌干达乳腺癌患者多柔比星药代动力学中亚治疗暴露:一项对个体化治疗具有重要意义的初步研究

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Abstract

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 AUC(0–24) 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.

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