PMID- 33829292
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210920
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 88
IP  - 1
DP  - 2021 Jul
TI  - Phase I study of tamibarotene monotherapy in pediatric and young adult patients 
      with recurrent/refractory solid tumors.
PG  - 99-107
LID - 10.1007/s00280-021-04271-9 [doi]
AB  - PURPOSE: Tamibarotene is a synthetic retinoid that inhibits proliferation and 
      induces differentiation of malignant cells by binding to the retinoic acid 
      receptor alpha/beta. Previous in vitro studies have shown that some pediatric solid 
      tumors with retinoic acid receptors differentiate in response to retinoic acid. 
      We conducted a phase I dose-escalation study to determine the recommended dose of 
      tamibarotene for further study in pediatric and young adult patients with 
      recurrent/refractory solid tumors. METHODS: Pediatric and young adult patients 
      with recurrent/refractory solid tumors were administered tamibarotene at 4, 6, 8, 
      10, and 12 mg/m(2)/day for 14 or 21 days of a 28 day cycle. Safety, efficacy, and 
      pharmacokinetics of tamibarotene were evaluated. RESULTS: Twenty-two patients 
      (median age 8 years) were enrolled in this study. No dose-limiting toxicity (DLT) 
      was encountered, and tamibarotene was generally well tolerated. Two patients 
      experienced severe adverse events (AEs), leading to discontinuation of the 
      treatment. One grade 4 venous thrombosis and one grade 2 erythema multiforme were 
      observed, which promptly resolved after tamibarotene discontinuance. The grade 4 
      venous thrombosis was a severe AE but not DLT because it occurred after the 
      evaluation period. Pharmacokinetic analyses showed a dose-dependent increase in 
      the maximum drug concentration (C(max)) and area under the concentration-time 
      curve (AUC). None of the patients achieved a complete response or partial 
      response. Seven patients had stable disease lasting longer than 18 weeks. 
      CONCLUSIONS: The recommended dose for phase II study of tamibarotene in pediatric 
      and young adult patients with refractory solid tumors is 12 mg/m(2)/day for 
      21 days in a 28 day cycle.
FAU - Nitani, Chika
AU  - Nitani C
AUID- ORCID: 0000-0002-1488-1326
AD  - Department of Pediatric Hematology and Oncology, Osaka City General Hospital, 
      2-13-22 Miyakojima-hondori, Miyakojima-ku, Osaka, 534-0021, Japan. 
      c-tanaka@med.osakacity-hp.or.jp.
FAU - Hara, Junichi
AU  - Hara J
AD  - Department of Pediatric Hematology and Oncology, Osaka City General Hospital, 
      2-13-22 Miyakojima-hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
FAU - Kawamoto, Hiroshi
AU  - Kawamoto H
AD  - Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Taguchi, Tomoaki
AU  - Taguchi T
AD  - Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Kimura, Toshimi
AU  - Kimura T
AD  - Department of Pharmacy, Tokyo Women's Medical University Hospital, Tokyo, Japan.
FAU - Yoshimura, Kenichi
AU  - Yoshimura K
AD  - Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima, 
      Japan.
FAU - Hamada, Akinobu
AU  - Hamada A
AD  - Division of Molecular Pharmacology, National Cancer Center Research Institute, 
      Tokyo, Japan.
FAU - Kitano, Shigehisa
AU  - Kitano S
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Hattori, Naoko
AU  - Hattori N
AD  - Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Ushijima, Toshikazu
AU  - Ushijima T
AD  - Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Ono, Hiromi
AU  - Ono H
AD  - Clinical Research Support Office, National Cancer Center Hospital East, Chiba, 
      Japan.
FAU - Nakamoto, Masako
AU  - Nakamoto M
AD  - Clinical Research Support Office, National Cancer Center Hospital East, Chiba, 
      Japan.
FAU - Higuchi, Tsukiko
AU  - Higuchi T
AD  - Clinical Research Support Office, National Cancer Center Hospital East, Chiba, 
      Japan.
FAU - Sato, Akihiro
AU  - Sato A
AD  - Clinical Research Support Office, National Cancer Center Hospital East, Chiba, 
      Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210407
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzoates)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 08V52GZ3H9 (tamibarotene)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antineoplastic Agents/*administration & dosage/pharmacokinetics
MH  - Benzoates/*administration & dosage/pharmacokinetics
MH  - Child
MH  - Child, Preschool
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Neoplasms/*drug therapy
MH  - Tetrahydronaphthalenes/*administration & dosage/pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - Dose-limiting toxicity
OT  - Pediatric and young adult solid tumors
OT  - Pharmacokinetics
OT  - Retinoic acid
OT  - Tamibarotene
EDAT- 2021/04/09 06:00
MHDA- 2021/09/21 06:00
CRDT- 2021/04/08 06:37
PHST- 2020/12/08 00:00 [received]
PHST- 2021/03/26 00:00 [accepted]
PHST- 2021/04/09 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/04/08 06:37 [entrez]
AID - 10.1007/s00280-021-04271-9 [pii]
AID - 10.1007/s00280-021-04271-9 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2021 Jul;88(1):99-107. doi: 
      10.1007/s00280-021-04271-9. Epub 2021 Apr 7.