Pharmacodynamic and Clinical Results from a Phase I/II Study of the HSP90 Inhibitor Onalespib in Combination with Abiraterone Acetate in Prostate Cancer.
Abiraterone Acetate
/ administration & dosage
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ pharmacokinetics
Benzamides
/ administration & dosage
HSP90 Heat-Shock Proteins
/ antagonists & inhibitors
Humans
Isoindoles
/ administration & dosage
Male
Middle Aged
Patient Safety
Prednisolone
/ administration & dosage
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Survival Rate
Tissue Distribution
Treatment Outcome
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
07
11
2018
revised:
01
02
2019
accepted:
17
05
2019
pubmed:
23
5
2019
medline:
15
9
2020
entrez:
23
5
2019
Statut:
ppublish
Résumé
Onalespib is a potent, fragment-derived second-generation HSP90 inhibitor with preclinical activity in castration-resistant prostate cancer (CPRC) models. This phase I/II trial evaluated onalespib in combination with abiraterone acetate (AA) and either prednisone or prednisolone (P) in men with CRPC progressing on AA/P. Patients with progressing CRPC were randomly assigned to receive 1 of 2 regimens of onalespib combined with AA/P. Onalespib was administered as intravenous infusion starting at 220 mg/m Forty-eight patients were treated with onalespib in combination with AA/P. The most common ≥grade 3 toxicities related to onalespib included diarrhea (21%) and fatigue (13%). Diarrhea was dose limiting at 260 and 160 mg/m Onalespib in combination with AA/P showed mild evidence of some biological effect; however, this effect did not translate into clinical activity, hence further exploration of this combination was not justified.
Identifiants
pubmed: 31113841
pii: 1078-0432.CCR-18-3212
doi: 10.1158/1078-0432.CCR-18-3212
pmc: PMC9081826
mid: NIHMS1798714
doi:
Substances chimiques
Benzamides
0
HSP90 Heat-Shock Proteins
0
Isoindoles
0
Prednisolone
9PHQ9Y1OLM
Abiraterone Acetate
EM5OCB9YJ6
(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone
Q7Y33N57ZZ
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
4624-4633Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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