Dovitinib (CHIR258, TKI258): Structure, development and preclinical and clinical activity

Camillo Porta, Palma Giglione, Wanda Liguigli, Chiara Paglino

Research output: Contribution to journalArticle

Abstract

Dovitinib is an oral multikinase inhibitor targeting FGF receptors, PDGF receptors and VEGF receptors. Its activity against FGF receptors suggests its usefulness in treating cancers after the failure of VEGF/VEGF receptor-targeting agents. The identified dose and schedule to be used in further studies was 500 mg orally for 5 days on and 2 days off. Biological considerations and the results achieved in a Phase I/II trial suggested its activity in advanced renal cell carcinoma patients pretreated with a tyrosine kinase inhibitor and an mTOR inhibitor. Surprisingly, in a randomized controlled Phase III trial versus sorafenib in the same setting, dovitinib failed to demonstrate any superiority. At present, dovitinib is being tested in different tumor types. However, molecular-based patient selection seems to be key to fully exploit the activity of this drug.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalFuture Oncology
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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Fibroblast Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
Platelet-Derived Growth Factor Receptors
Renal Cell Carcinoma
Protein-Tyrosine Kinases
Patient Selection
Vascular Endothelial Growth Factor A
Neoplasms
Appointments and Schedules
Pharmaceutical Preparations
4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
sorafenib

Keywords

  • Dovitinib
  • drug development
  • FGFR inhibitor
  • renal cell carcinoma
  • VEGFR inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Dovitinib (CHIR258, TKI258) : Structure, development and preclinical and clinical activity. / Porta, Camillo; Giglione, Palma; Liguigli, Wanda; Paglino, Chiara.

In: Future Oncology, Vol. 11, No. 1, 01.01.2015, p. 39-50.

Research output: Contribution to journalArticle

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