title: Flavopiridol in patients with relapsed or refractory multiple myeloma: a phase 2 trial with clinical and pharmacodynamic end-points.
abstract: Flavopiridol downregulates 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.
authors.affiliation: Mayo Clinic Rochester, MN 55905, USA. angela@mayo.edu
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Susan M
authors.initials: SM
authors.lastname: Geyer
authors.forename: Tom R
authors.initials: TR
authors.lastname: Fitch
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fenton
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Crescent R
authors.initials: CR
authors.lastname: Isham
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ziesmer
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Keith C
authors.initials: KC
authors.lastname: Bible
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000517:prevention & control*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib