A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors.


Journal

Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330

Informations de publication

Date de publication:
06 2020
Historique:
received: 08 03 2019
accepted: 31 05 2019
pubmed: 8 8 2019
medline: 2 6 2021
entrez: 8 8 2019
Statut: ppublish

Résumé

Background AT-101 is a BH3 mimetic that inhibits the heterodimerization of Bcl-2, Bcl-xL, Bcl-W, and Mcl-1 with pro-apoptotic proteins, thereby lowering the threshold for apoptosis. This phase I trial investigated the MTD of AT-101 in combination with paclitaxel and carboplatin in patients with advanced solid tumors. Methods Patients were treated with AT-101 (40 mg) every 12 h on days 1, 2 and 3 of each cycle combined with varying dose levels (DL) of paclitaxel and carboplatin [DL1: paclitaxel (150 mg/m

Identifiants

pubmed: 31388792
doi: 10.1007/s10637-019-00807-2
pii: 10.1007/s10637-019-00807-2
doi:

Substances chimiques

Proto-Oncogene Proteins c-bcl-2 0
Carboplatin BG3F62OND5
Caspase 3 EC 3.4.22.-
Gossypol KAV15B369O
Paclitaxel P88XT4IS4D
gossypol acetic acid S7RL72610R

Banques de données

ClinicalTrials.gov
['NCT00891072']

Types de publication

Clinical Trial, Phase I Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

855-865

Subventions

Organisme : NCI NIH HHS
ID : NCI CCSG 72720
Pays : United States
Organisme : NIH HHS
ID : U01CA132194
Pays : United States

Auteurs

Mark N Stein (MN)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA. mns2146@cumc.columbia.edu.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA. mns2146@cumc.columbia.edu.
Herbert Irving Comprehensive Cancer Center, 177 Fort Washington Ave, New York, NY, 10032, USA. mns2146@cumc.columbia.edu.

Susan Goodin (S)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Murugeson Gounder (M)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Darlene Gibbon (D)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Rebecca Moss (R)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Daniella Portal (D)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Diana Lindquist (D)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Yujie Zhao (Y)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Naoko Takebe (N)

Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA.

Antoinette Tan (A)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Joseph Aisner (J)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Hongxia Lin (H)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

Neal Ready (N)

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

Janice M Mehnert (JM)

Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA. mehnerja@rutger.cinj.edu.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA. mehnerja@rutger.cinj.edu.
Rutgers Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ, 08901, USA. mehnerja@rutger.cinj.edu.

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Classifications MeSH