PMID- 28879519
OWN - NLM
STAT- MEDLINE
DCOM- 20190125
LR  - 20221207
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 36
IP  - 2
DP  - 2018 Apr
TI  - Safety, tolerability, and pharmacokinetic profile of dabrafenib in Japanese 
      patients with BRAF (V600) mutation-positive solid tumors: a phase 1 study.
PG  - 259-268
LID - 10.1007/s10637-017-0502-8 [doi]
AB  - Background Dabrafenib is a BRAF inhibitor that has demonstrated clinical activity 
      with a good tolerability profile in patients with BRAF (V600E) mutated metastatic 
      melanoma. This study evaluated the safety and tolerability, pharmacokinetics and 
      preliminary efficacy of dabrafenib in Japanese patients. Methods This phase I, 
      open-label, dose escalation study was conducted in 12 Japanese patients with BRAF 
      (V600) mutation positive solid tumours. Primary endpoint was safety, assessed by 
      monitoring and recording of all adverse events (AEs), serious AEs, drug-related 
      AEs; secondary endpoints were pharmacokinetic profiles and efficacy measured by 
      tumour response. This study is registered with ClinicalTrials.gov, number 
      NCT01582997. Results Of the 12 patients enrolled, 3 each received 75 mg and 
      100 mg dabrafenib while 6 received 150 mg dabrafenib twice daily orally. Melanoma 
      and thyroid cancer were the primary tumours reported in 11 (92%) and 1 (8%) 
      patients respectively. Most AEs were grade 1 or 2 and considered related to study 
      treatment. Most common AEs reported in the 12 patients were alopecia in 7 (58%); 
      pyrexia, arthralgia and leukopenia in 6 (50%) each, hyperkeratosis and nausea in 
      4 (33%) each. Partial response as best overall response was reported in 7 of 12 
      (58%) patients and in 6 (55%) with malignant melanoma. No dose-limiting toxicity 
      (DLTs) were reported during the DLT evaluation periods. Conclusions Dabrafenib 
      was well tolerated and rapidly absorbed administered as single- or multiple dose. 
      Comparable safety and pharmacokinetic profiles were observed compared with 
      non-Japanese patients. Dabrafenib has promising clinical activity in Japanese 
      patients with BRAF mutated malignant melanoma.
FAU - Fujiwara, Yutaka
AU  - Fujiwara Y
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 
      Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. yutakafu@ncc.go.jp.
FAU - Yamazaki, Naoya
AU  - Yamazaki N
AD  - Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Kiyohara, Yoshio
AU  - Kiyohara Y
AD  - Dermatology Division, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
FAU - Yoshikawa, Shusuke
AU  - Yoshikawa S
AD  - Dermatology Division, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
FAU - Yamamoto, Noboru
AU  - Yamamoto N
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 
      Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
FAU - Tsutsumida, Arata
AU  - Tsutsumida A
AD  - Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Nokihara, Hiroshi
AU  - Nokihara H
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 
      Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
FAU - Namikawa, Kenjiro
AU  - Namikawa K
AD  - Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Mukaiyama, Akihira
AU  - Mukaiyama A
AD  - Development Department, Novartis Pharma K.K, Tokyo, Japan.
FAU - Zhang, Fanghong
AU  - Zhang F
AD  - Development Department, Novartis Pharma K.K, Tokyo, Japan.
FAU - Tamura, Tomohide
AU  - Tamura T
AD  - Thoracic Center, St. Luke's International Hospital, Tokyo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT01582997
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170907
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Imidazoles)
RN  - 0 (Oximes)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - QGP4HA4G1B (dabrafenib)
SB  - IM
MH  - Adult
MH  - *Asian People
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Imidazoles/administration & dosage/*adverse effects/*pharmacokinetics/therapeutic 
      use
MH  - Male
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Neoplasms/*drug therapy/*genetics
MH  - Oximes/administration & dosage/*adverse effects/*pharmacokinetics/therapeutic use
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Treatment Outcome
OTO - NOTNLM
OT  - BRAF V600
OT  - Dabrafenib
OT  - Japanese
OT  - Malignant melanoma
OT  - Mutation
OT  - Solid tumor
EDAT- 2017/09/08 06:00
MHDA- 2019/01/27 06:00
CRDT- 2017/09/08 06:00
PHST- 2017/07/12 00:00 [received]
PHST- 2017/08/11 00:00 [accepted]
PHST- 2017/09/08 06:00 [pubmed]
PHST- 2019/01/27 06:00 [medline]
PHST- 2017/09/08 06:00 [entrez]
AID - 10.1007/s10637-017-0502-8 [pii]
AID - 10.1007/s10637-017-0502-8 [doi]
PST - ppublish
SO  - Invest New Drugs. 2018 Apr;36(2):259-268. doi: 10.1007/s10637-017-0502-8. Epub 
      2017 Sep 7.