Flavopiridol in patients with relapsed or refractory multiple myeloma: A phase 2 trial with clinical and pharmacodynamic end-points

Angela Dispenzieri, Morie A. Gertz, Martha Q. Lacy, Susan M. Geyer, Tom R. Fitch, Robert G. Fenton, Rafael Fonseca, Crescent R. Isham, Steven C. Ziesmer, Charles Erlichman, Keith C. Bible

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Flavopiridol down regulates anti-apoptotic regulators including Mcl-1, upregulates p53, globally attenuates transcription through inhibition of P-TEFb, binds to DNA, and inhibits angiogenesis. Eighteen myeloma patients were treated with 1-hour flavopiridol infusions for 3 consecutive days every 21 days. Immunoblotting for Mcl-1, Bcl-2, p53, cyclin D, phosphoRNA polymerase II and phosphoSTAT 3 was conducted on myeloma cells. Ex vivo flavopiridol treatment of cells resulted in cytotoxicity, but only after longer exposure times at higher flavopiridol concentrations than were anticipated to be achieved in vivo. No anti-myeloma activity was observed in vivo. As administered, flavopiridol has disappointing activity as a single agent in advanced myeloma.

Original languageEnglish (US)
Pages (from-to)390-393
Number of pages4
JournalHaematologica
Volume91
Issue number3
StatePublished - Mar 1 2006

Keywords

  • Clinical trial
  • Mcl-1
  • Therapy

ASJC Scopus subject areas

  • Hematology

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