Abstract | BACKGROUND:
Tivantinib (formerly ARQ 197) is a selective inhibitor of c-Met mainly metabolized by CYP2C19. CYP2C19 is known for genetic polymorphisms, and ~20% of Asians are poor metabolizers (PMs), while others are extensive metabolizers (EMs). In this study, we examined the safety, pharmacokinetics (PK), and preliminary efficacy of tivantinib as a single agent to determine recommended phase II doses (RPIIDs). PATIENTS AND METHODS: Forty-seven patients (EMs, 33; PMs, 14) with solid tumors were orally treated with tivantinib, from 70 to 360 mg bid in a 3 + 3 dose-escalation scheme. EMs and PMs were separately enrolled at the doses >120 mg bid. RESULTS: CONCLUSION: Two different settings of RPIIDs, 360 mg bid for EMs and 240 mg bid for PMs, were determined.
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Authors | N Yamamoto, H Murakami, T Nishina, T Hirashima, K Sugio, K Muro, T Takahashi, T Naito, H Yasui, S Akinaga, Y Koh, N Boku |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 24
Issue 6
Pg. 1653-9
(Jun 2013)
ISSN: 1569-8041 [Electronic] England |
PMID | 23413279
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
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Chemical References |
- ARQ 197
- Pyrrolidinones
- Quinolines
- Aryl Hydrocarbon Hydroxylases
- CYP2C19 protein, human
- Cytochrome P-450 CYP2C19
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Topics |
- Aryl Hydrocarbon Hydroxylases
(genetics)
- Cohort Studies
- Cytochrome P-450 CYP2C19
- Dose-Response Relationship, Drug
- Female
- Gastrointestinal Diseases
(chemically induced, enzymology, genetics)
- Humans
- Male
- Middle Aged
- Neoplasms
(drug therapy, enzymology, genetics)
- Polymorphism, Genetic
(genetics)
- Pyrrolidinones
(adverse effects, pharmacokinetics, therapeutic use)
- Quinolines
(adverse effects, pharmacokinetics, therapeutic use)
- Treatment Outcome
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