PMID- 29238851
OWN - NLM
STAT- MEDLINE
DCOM- 20190122
LR  - 20221207
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 81
IP  - 2
DP  - 2018 Feb
TI  - Phase I/II study of mocetinostat in combination with gemcitabine for patients 
      with advanced pancreatic cancer and other advanced solid tumors.
PG  - 355-364
LID - 10.1007/s00280-017-3494-3 [doi]
AB  - PURPOSE: To evaluate the safety and efficacy of mocetinostat (a Class I/IV HDAC 
      inhibitor) in combination with gemcitabine in patients with solid tumors, 
      including pancreatic cancer. METHODS: In this open-label, non-randomized Phase 
      I/II study (NCT00372437) sequential cohorts of patients with solid tumors 
      received gemcitabine (1000 mg/m(2), day 1 of three consecutive weeks, 4-week 
      cycles) and oral mocetinostat [50-110 mg, three times per week (TIW)]. The 
      maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) was determined 
      based on dose-limiting toxicities in Cycle 1 (Phase I study). The MTD/RP2D was 
      further evaluated in patients with advanced pancreatic cancer (Phase II study) 
      using a two-stage design. The Phase II primary endpoint was overall response rate 
      (ORR). RESULTS: Forty-eight patients were enrolled into the Phase I (n = 25) and 
      Phase II (n = 23) studies. In the Phase I study, the MTD/RP2D was mocetinostat 
      90 mg TIW + gemcitabine 1000 mg/m(2). Grade >/= 3 treatment-related adverse events 
      (AEs) were reported by 81% of all patients, the most frequent being fatigue (38%) 
      and thrombocytopenia (19%). The ORR was 11% in the Phase I study (n = 2 patients 
      with pancreatic cancer, responses lasting for 16.8 and 4.0 months, respectively). 
      As no responses were seen in the Phase II cohort, the study was terminated. 
      CONCLUSIONS: Mocetinostat TIW in combination with gemcitabine was associated with 
      significant toxicities in patients with advanced pancreatic cancer. The level of 
      clinical activity of this treatment combination was not considered high enough to 
      merit further testing in this setting.
FAU - Chan, Emily
AU  - Chan E
AD  - Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
FAU - Chiorean, E Gabriela
AU  - Chiorean EG
AD  - Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, 
      USA.
AD  - Indiana University Cancer Center, Indianapolis, IN, USA.
FAU - O'Dwyer, Peter J
AU  - O'Dwyer PJ
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Gabrail, Nashat Y
AU  - Gabrail NY
AD  - Gabrail Cancer Center, Canton, OH, USA.
FAU - Alcindor, Thierry
AU  - Alcindor T
AD  - McGill University Health Centre, Montreal, QC, Canada.
FAU - Potvin, Diane
AU  - Potvin D
AD  - Mirati Therapeutics Inc., 9393 Towne Centre Drive, Suite 200, San Diego, CA, 
      92121, USA.
FAU - Chao, Richard
AU  - Chao R
AD  - Mirati Therapeutics Inc., 9393 Towne Centre Drive, Suite 200, San Diego, CA, 
      92121, USA. chaor@MIRATI.COM.
FAU - Hurwitz, Herbert
AU  - Hurwitz H
AD  - Duke University Medical Center, Durham, NC, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171213
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Benzamides)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0W860991D6 (Deoxycytidine)
RN  - A6GWB8T96J (mocetinostat)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antimetabolites, Antineoplastic/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Benzamides/administration & dosage
MH  - Cohort Studies
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - Endpoint Determination
MH  - Female
MH  - Histone Deacetylase Inhibitors/administration & dosage
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/drug therapy
MH  - Pancreatic Neoplasms/*drug therapy
MH  - Pyrimidines/administration & dosage
MH  - Treatment Outcome
MH  - Gemcitabine
OTO - NOTNLM
OT  - Gemcitabine
OT  - Histone deacetyltransferase
OT  - Mocetinostat
OT  - Pancreatic cancer
OT  - Pharmacodynamics
OT  - Phase 2
EDAT- 2017/12/15 06:00
MHDA- 2019/01/23 06:00
CRDT- 2017/12/15 06:00
PHST- 2017/10/27 00:00 [received]
PHST- 2017/11/27 00:00 [accepted]
PHST- 2017/12/15 06:00 [pubmed]
PHST- 2019/01/23 06:00 [medline]
PHST- 2017/12/15 06:00 [entrez]
AID - 10.1007/s00280-017-3494-3 [pii]
AID - 10.1007/s00280-017-3494-3 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2018 Feb;81(2):355-364. doi: 
      10.1007/s00280-017-3494-3. Epub 2017 Dec 13.