Drug-drug interactions in metastatic hormone-sensitive prostate cancer (mHSPC): practical considerations for treating men with androgen receptor pathway inhibitors and common medications in this stage.

David Conde-Estévez, Fernando López-Campos, Cristina Ibáñez, Manuel Tourís-Lores, Álvaro Montesa, Emilio Ríos, Paola Usán, Cristina Moretones

Journal: Expert opinion on drug metabolism & toxicology 2025;21(6):625-636

PMID: 40087028

Abstract

INTRODUCTION

New androgen receptor pathway inhibitors (ARPIs) are an essential part of the treatment strategy for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Despite the good tolerability of ARPIs, after treatment is started, drug-drug interactions (DDIs) between these and other medications frequently taken by these patients may appear. DDIs may reduce the therapeutic effect of both and lead to increased adverse events. DDIs should be carefully assessed before an ARPI is started.

AREAS COVERED

We first review the current therapeutic landscape for mHSPC, common age-related comorbidities and other comorbidities or adverse events arising from previous or current treatments for prostate cancer, and patients' symptomatology. We then analyze the potential toxicities arising from medications for these conditions and those of mHSPC: ARPIs (abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and darolutamide) and docetaxel.

EXPERT OPINION

Before mHSPC patients are treated with an ARPI, careful assessment of patient eligibility for each treatment alternative and potential DDIs between these and treatments for current comorbidities is a fundamental component in clinical decision-making. ARPIs with low potential DDIs allow keeping current concomitant medications without significant relevant dose adjustments and help reduce the risk of toxicities and comorbidity-related decompensation.

Address: Department of Pharmacy, Institut Català d'Oncologia, Barcelona, Spain.; Blanquerna School of Health Sciences, Universidad Ramon Llull, Barcelona, Spain.; Department of Pharmacy, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela, Spain.; Medical Oncology Department, Hospital Regional de Málaga, IBIMA, Málaga, Spain.; Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain.; Department of Radiation Oncology, GenesisCare Vithas La Milagrosa, Madrid, Spain.; Department of Urology, Hospital Universitario La Paz-IdiPaz, Universidad Autónoma de Madrid, Madrid, Spain.; Medical Department Oncology, Bayer Hispania S.L, Barcelona, Spain.; Department of Pharmacy, Hospital Del Mar, Barcelona, Spain.; Cancer Research Programme, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
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