Phase 1 study of veliparib (ABT-888), a poly (ADP-ribose) polymerase inhibitor, with carboplatin and paclitaxel in advanced solid malignancies.
Administration, Oral
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Benzimidazoles
/ administration & dosage
Carboplatin
/ administration & dosage
Drug Administration Schedule
Drug Resistance, Neoplasm
/ drug effects
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
/ drug therapy
Paclitaxel
/ pharmacokinetics
Poly (ADP-Ribose) Polymerase-1
/ antagonists & inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
/ administration & dosage
Treatment Outcome
Advanced cancer
Carboplatin
Clinical trial
Paclitaxel
Phase 1
Poly(ADP-ribose) polymerase
Veliparib
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
18
08
2019
accepted:
05
09
2019
pubmed:
25
9
2019
medline:
28
5
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
Veliparib is an oral inhibitor of poly (ADP-ribose) polymerase (PARP)-1 and -2. PARP-1 expression may be increased in cancer, and this increase confers resistance to cytotoxic agents. We aimed to determine the recommended phase 2 dose (RP2D), maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics (PK) of veliparib combined with paclitaxel and carboplatin. Eligibility criteria included patients with advanced solid tumors treated with ≤ 3 prior regimens. Paclitaxel and carboplatin were administered on day 3 of a 21-day cycle. Veliparib was given PO BID days 1-7, except for cycle 1 in the first 46 patients to serve as control for toxicity and PK. A standard "3 + 3" design started veliparib at 10 mg BID, paclitaxel at 150 mg/m Seventy-three patients were enrolled. Toxicities were as expected with carboplatin/paclitaxel chemotherapy, including neutropenia, thrombocytopenia, and peripheral neuropathy. DLTs were seen in two of seven evaluable patients at the maximum administered dose (MAD): veliparib 120 mg BID, paclitaxel 200 mg/m Veliparib, paclitaxel, and carboplatin were well tolerated and demonstrated promising antitumor activity.
Identifiants
pubmed: 31549216
doi: 10.1007/s00280-019-03960-w
pii: 10.1007/s00280-019-03960-w
pmc: PMC7825275
mid: NIHMS1540512
doi:
Substances chimiques
Benzimidazoles
0
Poly(ADP-ribose) Polymerase Inhibitors
0
veliparib
01O4K0631N
Carboplatin
BG3F62OND5
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Paclitaxel
P88XT4IS4D
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1289-1301Subventions
Organisme : NCI NIH HHS
ID : UM1 CA186690
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA099168
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186717
Pays : United States
Organisme : NCI NIH HHS
ID : UM1-CA186690
Pays : United States
Organisme : NCI NIH HHS
ID : U01-CA099168
Pays : United States
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