Pharmacokinetics and safety of rucaparib in patients with advanced solid tumors and hepatic impairment.


Journal

Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519

Informations de publication

Date de publication:
08 2021
Historique:
received: 03 12 2020
accepted: 14 04 2021
pubmed: 29 4 2021
medline: 18 9 2021
entrez: 28 4 2021
Statut: ppublish

Résumé

The poly(ADP-ribose) polymerase inhibitor rucaparib is approved for the treatment of patients with recurrent ovarian and metastatic castration-resistant prostate cancer; however, limited data are available on its use in patients with hepatic dysfunction. This study investigated whether hepatic impairment affects the pharmacokinetics, safety, and tolerability of rucaparib in patients with advanced solid tumors. Patients with normal hepatic function or moderate hepatic impairment according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria were enrolled and received a single oral dose of rucaparib 600 mg. Concentrations of rucaparib and its metabolite M324 in plasma and urine were measured. Pharmacokinetic parameters were compared between hepatic function groups, and safety and tolerability were assessed. Sixteen patients were enrolled (n = 8 per group). Rucaparib maximum concentration (C Patients with moderate hepatic impairment showed mildly increased AUC

Identifiants

pubmed: 33909097
doi: 10.1007/s00280-021-04278-2
pii: 10.1007/s00280-021-04278-2
pmc: PMC8236452
doi:

Substances chimiques

Antineoplastic Agents 0
Indoles 0
Poly(ADP-ribose) Polymerase Inhibitors 0
rucaparib 8237F3U7EH

Types de publication

Clinical Trial, Phase I Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

259-270

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Auteurs

Nikolay Grechko (N)

Clinical Science, Clovis Oncology UK Ltd., Cambridge, UK.

Viera Skarbova (V)

Department of Internal Medicine and Clinical Pharmacology, Summit Clinical Research, Bratislava, Slovakia.

Monika Tomaszewska-Kiecana (M)

BioVirtus Centrum Medyczne, Jozefow, Poland.

Rodryg Ramlau (R)

Department of Oncology and Pulmonology, Poznan University of Medical Sciences, Poznan, Poland.

Piotr Centkowski (P)

Department of Oncology, Provincial Specialist Hospital in Biała Podlaska, Biała Podlaska, Poland.

Yvette Drew (Y)

Clinical and Translational Institute, Newcastle University, Newcastle Upon Tyne, UK.

Rafal Dziadziuszko (R)

Department of Oncology and Radiotherapy and Early Clinical Trials Unit, Medical University of Gdańsk, Gdańsk, Poland.

Milada Zemanova (M)

Department of Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Jeri Beltman (J)

Regulatory Affairs, Clovis Oncology, Inc., Boulder, CO, USA.

Eileen Nash (E)

Clinical Operations, Clovis Oncology, Inc., Boulder, CO, USA.

Jenn Habeck (J)

Biostatistics, Clovis Oncology, Inc., Boulder, CO, USA.

Mingxiang Liao (M)

Clinical Pharmacology, Clovis Oncology, Inc., 5500 Flatiron Pkwy, Boulder, CO, 80301, USA.

Jim Xiao (J)

Clinical Pharmacology, Clovis Oncology, Inc., 5500 Flatiron Pkwy, Boulder, CO, 80301, USA. jxiao@clovisoncology.com.

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Classifications MeSH