PMID- 24169346
OWN - NLM
STAT- MEDLINE
DCOM- 20140211
LR  - 20221207
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 109
IP  - 11
DP  - 2013 Nov 26
TI  - CYP2C19 genotype-based phase I studies of a c-Met inhibitor tivantinib in 
      combination with erlotinib, in advanced/metastatic non-small cell lung cancer.
PG  - 2803-9
LID - 10.1038/bjc.2013.588 [doi]
AB  - BACKGROUND: A previous clinical study in non-small cell lung cancer (NSCLC) 
      patients in Western countries suggested the potential for combination of a 
      first-in-class non-ATP-competitive c-Met inhibitor tivantinib with an epidermal 
      growth factor receptor-tyrosine kinase inhibitor erlotinib. Polymorphisms of 
      CYP2C19, the key metabolic enzyme for tivantinib, should be addressed to 
      translate the previous Western study to Asian population, because higher 
      incidence of poor metabolisers (PMs) is reported in Asian population. METHODS: 
      Japanese patients with advanced/metastatic NSCLC received tivantinib in 
      combination with erlotinib to evaluate safety and pharmacokinetics. Doses of 
      tivantinib were escalated separately for extensive metabolisers (EMs) and PMs. 
      RESULTS: Tivantinib, when combined with erlotinib, was well tolerated up to 360 
      mg BID for EMs and 240 mg BID for PMs, respectively. Among 25 patients (16 EMs 
      and 9 PMs), the adverse events (AEs) related to tivantinib and/or erlotinib 
      (>20%, any grade) were rash, diarrhoea, dry skin and nausea. Grade >/=3 AEs were 
      leukopenia, anaemia and neutropenia. No dose-limiting toxicity was observed. 
      Pharmacokinetics profile of tivantinib was not clearly different between the 
      combination and monotherapy. Three partial response and three long-term stable 
      disease (>/=24 weeks) were reported. CONCLUSION: Two doses of tivantinib in 
      combination with erlotinib were recommended based on CYP2C19 genotype: 360 mg BID 
      for EMs and 240 mg BID for PMs.
FAU - Yamamoto, N
AU  - Yamamoto N
AD  - Division of Thoracic Oncology, Shizuoka Cancer Center, 1007, Shimonagakubo, 
      Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
FAU - Murakami, H
AU  - Murakami H
FAU - Hayashi, H
AU  - Hayashi H
FAU - Fujisaka, Y
AU  - Fujisaka Y
FAU - Hirashima, T
AU  - Hirashima T
FAU - Takeda, K
AU  - Takeda K
FAU - Satouchi, M
AU  - Satouchi M
FAU - Miyoshi, K
AU  - Miyoshi K
FAU - Akinaga, S
AU  - Akinaga S
FAU - Takahashi, T
AU  - Takahashi T
FAU - Nakagawa, K
AU  - Nakagawa K
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20131029
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (ARQ 197)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Quinazolines)
RN  - 0 (Quinolines)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2C19 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/*therapeutic use
MH  - Aryl Hydrocarbon Hydroxylases/*genetics
MH  - Asian People
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/ethnology/genetics/pathology
MH  - Cytochrome P-450 CYP2C19
MH  - Disease Progression
MH  - Drug Dosage Calculations
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/ethnology/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Proto-Oncogene Proteins c-met/antagonists & inhibitors
MH  - Pyrrolidinones/*administration & dosage/adverse effects/pharmacokinetics
MH  - Quinazolines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Quinolines/*administration & dosage/adverse effects/pharmacokinetics
PMC - PMC3844902
EDAT- 2013/10/31 06:00
MHDA- 2014/02/12 06:00
PMCR- 2014/11/26
CRDT- 2013/10/31 06:00
PHST- 2013/05/27 00:00 [received]
PHST- 2013/08/23 00:00 [revised]
PHST- 2013/09/04 00:00 [accepted]
PHST- 2013/10/31 06:00 [entrez]
PHST- 2013/10/31 06:00 [pubmed]
PHST- 2014/02/12 06:00 [medline]
PHST- 2014/11/26 00:00 [pmc-release]
AID - bjc2013588 [pii]
AID - 10.1038/bjc.2013.588 [doi]
PST - ppublish
SO  - Br J Cancer. 2013 Nov 26;109(11):2803-9. doi: 10.1038/bjc.2013.588. Epub 2013 Oct 
      29.