PMID- 33602316
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210920
IS  - 2162-3619 (Print)
IS  - 2162-3619 (Electronic)
IS  - 2162-3619 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Feb 18
TI  - Belinostat in combination with standard cyclophosphamide, doxorubicin, 
      vincristine and prednisone as first-line treatment for patients with newly 
      diagnosed peripheral T-cell lymphoma.
PG  - 15
LID - 10.1186/s40164-021-00203-8 [doi]
LID - 15
AB  - BACKGROUND: Belinostat is a histone deacetylase inhibitor approved for relapsed 
      refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study 
      was to determine the maximum tolerated dose (MTD) of belinostat combined with 
      CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall 
      response rate (ORR), and belinostat pharmacokinetics (PK). METHODS: Patients 
      were >/= 18 years with histologically confirmed, previously untreated PTCL. 
      Patients received belinostat (1000 mg/m(2) once daily) + standard CHOP for 6 
      cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled 
      patients at MTD dose. RESULTS: Twenty-three patients were treated. One patient 
      experienced DLT (Grade 3 non-hematologic toxicity) on Day 1-3 schedule, resulting 
      in escalation to Day 1-5 schedule (n = 3). No DLTs were observed and Day 1-5 
      schedule with 1000 mg/m(2) was declared as MTD. Twelve additional patients were 
      enrolled in Part B using MTD. Median relative dose intensity was 98%. All 
      patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), 
      and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) 
      and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK 
      parameters were similar to single-agent. CONCLUSIONS: Bel-CHOP was well tolerated 
      and MTD in CHOP combination was the same dose and schedule as single agent 
      dosing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01839097.
FAU - Johnston, Patrick B
AU  - Johnston PB
AD  - Mayo Clinic, 200 first St SW, Rochester, MN, 55905, USA. 
      johnston.patrick@mayo.edu.
FAU - Cashen, Amanda F
AU  - Cashen AF
AD  - Division of Oncology, Washington University Medical School, 660 S. Euclid Ave, 
      Campus, Box 8007, St Louis, MO, 63110, USA.
FAU - Nikolinakos, Petros G
AU  - Nikolinakos PG
AD  - University Cancer and Blood Center, 3320 Old Jefferson Rd #700, Athens, GA, 
      30607, USA.
FAU - Beaven, Anne W
AU  - Beaven AW
AD  - Duke University School of Medicine, 2592 Morris Bldg, Box 3406, Durham, NC, 
      27710, USA.
FAU - Barta, Stefan Klaus
AU  - Barta SK
AD  - Dept of Hematology/Oncology, Fox Chase Cancer Center, 333 Cottman Ave, 
      Philadelphia, PA, 19111, USA.
FAU - Bhat, Gajanan
AU  - Bhat G
AD  - Spectrum Pharmaceuticals, 157 Technology Dr, Irvine, CA, 92618, USA.
FAU - Hasal, Steven J
AU  - Hasal SJ
AD  - Spectrum Pharmaceuticals, 157 Technology Dr, Irvine, CA, 92618, USA.
FAU - De Vos, Sven
AU  - De Vos S
AD  - Cancer Care, Ronald Reagan University of California At Los Angeles Medical 
      Center, 2020 Santa Monica Blvd, Santa Monica, CA, 90404, USA.
FAU - Oki, Yasuhiro
AU  - Oki Y
AD  - Dept of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, 1515 
      Holcombe Blvd, Unit 0429, Houston, TX, 77030, USA.
FAU - Deng, Changchun
AU  - Deng C
AD  - Center for Lymphoid Malignancies, Columbia University Medical Center, 51 West 
      51st St, New York, NY, 10019, USA.
FAU - Foss, Francine M
AU  - Foss FM
AD  - Medical Oncology, Yale Cancer Center, 333 Cedar St, TMP 3, PO Box 208028, New 
      Haven, CT, 06510, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01839097
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20210218
PL  - England
TA  - Exp Hematol Oncol
JT  - Experimental hematology & oncology
JID - 101590676
PMC - PMC7893947
OTO - NOTNLM
OT  - Belinostat
OT  - CHOP
OT  - Histone deacetylase inhibitor (HDACi)
OT  - Peripheral T-cell lymphoma (PTCL)
COIS- A.C has received funding from Celgene, and is part of the Speaker's Bureau for 
      Seattle Genetics and Novartis. S.B. has received research funding from Seattle 
      Genetics. G.B, G.R, S.H are employees of Spectrum Pharmaceuticals. F.F. has been 
      a consultant, Speakers Bureau and received research funding from Spectrum 
      Pharmaceuticals, Celgene, Seattle Genetics, Infinity, Millennium. The remaining 
      authors declare that they have no conflict of interest.
EDAT- 2021/02/20 06:00
MHDA- 2021/02/20 06:01
PMCR- 2021/02/18
CRDT- 2021/02/19 05:42
PHST- 2020/10/05 00:00 [received]
PHST- 2021/01/22 00:00 [accepted]
PHST- 2021/02/19 05:42 [entrez]
PHST- 2021/02/20 06:00 [pubmed]
PHST- 2021/02/20 06:01 [medline]
PHST- 2021/02/18 00:00 [pmc-release]
AID - 10.1186/s40164-021-00203-8 [pii]
AID - 203 [pii]
AID - 10.1186/s40164-021-00203-8 [doi]
PST - epublish
SO  - Exp Hematol Oncol. 2021 Feb 18;10(1):15. doi: 10.1186/s40164-021-00203-8.