PMID- 28915584
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 34
DP  - 2017 Aug 22
TI  - A phase 1 dose-escalation study of the oral histone deacetylase inhibitor 
      abexinostat in combination with standard hypofractionated radiotherapy in 
      advanced solid tumors.
PG  - 56199-56209
LID - 10.18632/oncotarget.14147 [doi]
AB  - Current treatments for advanced solid tumors tend to be only palliative. Although 
      radiotherapy is administered with a curative intent, radioresistance and 
      dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral 
      pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation 
      in various solid tumor cell lines. We conducted an exploratory, phase 1, 
      dose-escalation study of abexinostat in combination with standard 
      hypofractionated radiotherapy in patients with advanced solid tumors treated in a 
      palliative setting. Among 58 treated patients, the median age was 61.5 years 
      (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received 
      previous chemotherapy alone or chemotherapy in combination with surgery and/or 
      radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m(2) (140 
      mg). Of the 51 patients evaluable for response, best overall response was 8% (1 
      complete response [CR], 3 partial responses [PRs]), and best loco-regional 
      response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, 
      patients with target or non-target brain lesions showed encouraging responses, 
      with 1 patient achieving a best loco-regional response of CR. Treatment-emergent 
      grade >/=3 adverse events (AEs) were few, with most common being thrombocytopenia 
      (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued 
      treatment due to AEs. No grade >/=3 prolongation of the QTc interval was observed, 
      with no treatment discontinuations due to this AE. Oral abexinostat combined with 
      radiotherapy was well tolerated in patients with advanced solid tumors. The 
      combination may have potential for treatment of patients with brain lesions.
FAU - Deutsch, Eric
AU  - Deutsch E
AD  - Department of Radiation Oncology, Gustave-Roussy Cancer Campus, Villejuif, 
      France.
AD  - INSERM 1030 Molecular Radiotherapy, Villejuif, France.
AD  - Faculte de Medecine, Universite Paris-Sud, Universite Paris-Saclay, Le 
      Kremlin-Bicetre, France.
FAU - Moyal, Elizabeth Cohen-Jonathan
AU  - Moyal EC
AD  - Department of Radiation Oncology, Institut Claudius Regaud, Toulouse, France.
FAU - Gregorc, Vanesa
AU  - Gregorc V
AD  - Department of Medical Oncology, Istituto di Ricovero e Cura a Carattere 
      Scientifico, Ospedale San Raffaele, Milan, Italy.
FAU - Zucali, Paolo Andrea
AU  - Zucali PA
AD  - Department of Medical Oncology and Haematology, Humanitas Cancer Center, IRCCS, 
      Rozzano, Italy.
FAU - Menard, Jean
AU  - Menard J
AD  - Department of Radiation Oncology, Hopital Saint-Louis, Paris, France.
FAU - Soria, Jean-Charles
AU  - Soria JC
AD  - DITEP (Departement d'Innovations Therapeutiques et Essais Precoces), Gustave 
      Roussy Cancer Campus, Villejuif, France.
FAU - Kloos, Ioana
AU  - Kloos I
AD  - Institut de Recherches Internationales Servier, Clinical Pharmacokinetics, 
      Suresnes, France.
FAU - Hsu, Jeff
AU  - Hsu J
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.
FAU - Luan, Ying
AU  - Luan Y
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.
FAU - Liu, Emily
AU  - Liu E
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.
FAU - Vezan, Remus
AU  - Vezan R
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.
FAU - Graef, Thorsten
AU  - Graef T
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.
FAU - Rivera, Sofia
AU  - Rivera S
AD  - Department of Radiation Oncology, Gustave-Roussy Cancer Campus, Villejuif, 
      France.
AD  - INSERM 1030 Molecular Radiotherapy, Villejuif, France.
AD  - Faculte de Medecine, Universite Paris-Sud, Universite Paris-Saclay, Le 
      Kremlin-Bicetre, France.
LA  - eng
PT  - Journal Article
DEP - 20161224
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5593555
OTO - NOTNLM
OT  - abexinostat
OT  - brain lesions
OT  - histone deacetylase inhibitor
OT  - radiotherapy
OT  - solid tumors
COIS- CONFLICTS OF INTEREST ED, consulting or advisory role for Roche, research funding 
      from Servier, Roche, AstraZeneca, travel accommodations from Merck, Roche; ECJM, 
      consulting or advisory role for Merck; VG, consulting or advisory role for and 
      travel accommodations from Pfizer, Novartis, Eli Lilly, Roche, AstraZeneca, 
      Boehringer Ingelheim; PAZ, no relevant financial disclosures; JM, no relevant 
      financial disclosures; JCS, no relevant financial disclosures; IK, patients, 
      royalties, or other intellectual property for Servier; JH, employment with 
      Pharmacyclics and Astellas Pharma (Agensys), stock or other ownership for AbbVie; 
      YL, employment with Pharmacyclics, stock or other ownership for AbbVie; EL, 
      employment for Pharmacyclics, Theorem Clinical Research, stock or other ownership 
      for AbbVie; RV, employment for Pharmacyclics, stock or other ownership for 
      AbbVie; TG, employment and patents, royalties, or other intellectual property for 
      Pharmacyclics, stock or other ownership for AbbVie; SR, travel accommodations 
      from Novartis.
EDAT- 2017/09/17 06:00
MHDA- 2017/09/17 06:01
PMCR- 2017/08/22
CRDT- 2017/09/17 06:00
PHST- 2016/07/28 00:00 [received]
PHST- 2016/11/14 00:00 [accepted]
PHST- 2017/09/17 06:00 [entrez]
PHST- 2017/09/17 06:00 [pubmed]
PHST- 2017/09/17 06:01 [medline]
PHST- 2017/08/22 00:00 [pmc-release]
AID - 14147 [pii]
AID - 10.18632/oncotarget.14147 [doi]
PST - epublish
SO  - Oncotarget. 2016 Dec 24;8(34):56199-56209. doi: 10.18632/oncotarget.14147. 
      eCollection 2017 Aug 22.