Toxicities of PARP inhibitors in genitourinary cancers.

Shahrokh F Shariat, Tibor Szarvas, Péter Nyirády, Tamás Fazekas, Marcin Miszczyk, János Szalontai

Journal: Current opinion in urology 2025;35(4):467-471

PMID: 40336260

Free Full Text on PubMed Central View on PubMed

Abstract

PURPOSE OF REVIEW

Recent advancements in the understanding of the genetic background of genitourinary cancers allowed for a successful introduction of targeted antitumor agents to prostate cancer (PCa) treatment. Inhibitors of the poly ADP-ribose polymerase enzyme (PARPi) transformed the treatment landscape of metastatic prostate cancer, and being increasingly studied in earlier disease stages. However, they are associated with nonnegligible toxicity, therefore, we aimed to summarize their side-effect profile in patients with PCa.

RECENT FINDINGS

Hematologic toxicities, particularly anemia, thrombocytopenia, and neutropenia are among the most common and serious adverse events associated with PARPi, highlighting the need for regular blood count monitoring. Nonhematologic side effects, including fatigue, nausea, vomiting, diarrhea, and constipation, are common, and can be mitigated with supportive interventions like dietary modifications, antiemetics, or stool management techniques. Special attention should be given to patients with therapy-resistant or persistent cytopenia, in whom bone marrow biopsy should be considered, as it can indicate myelodysplastic syndrome and acute myeloid leukemia.

SUMMARY

PARP inhibitors represent a major advancement in the management of metastatic prostate cancer, offering a significant survival benefit in applicable cases. However, patients need to be carefully selected and informed, to allow for optimal balancing between the benefits and nonneglectable risks of severe toxicities. Better understanding of PARPi toxicity profile can improve personalized decision-making and enhance treatment compliance, through raising patients' awareness about the possible side effects of PARPi.

Address: Department of Urology, Semmelweis University, Budapest, Hungary.; Department of Urology, Semmelweis University, Budapest, Hungary.; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.; Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.; Collegium Medicum - Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland.; Department of Urology, Semmelweis University, Budapest, Hungary.; Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.; Department of Urology, Weill Cornell Medical College, New York, New York, USA.; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.; Research Centre for Evidence Medicine, Urology Department, Tabriz University of Medical Sciences, Tabriz, Iran.; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.; Department of Urology, Semmelweis University, Budapest, Hungary.; Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.

DOI: 10.1097/MOU.0000000000001297