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

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 journal › Article › peer-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 language	English (US)
Pages (from-to)	390-393
Number of pages	4
Journal	Haematologica
Volume	91
Issue number	3
State	Published - Mar 2006

Keywords

Clinical trial
Mcl-1
Therapy

ASJC Scopus subject areas

Hematology

Cite this

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

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.",

keywords = "Clinical trial, Mcl-1, Therapy",

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

year = "2006",

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language = "English (US)",

volume = "91",

pages = "390--393",

journal = "Haematologica",

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AU - Dispenzieri, Angela

AU - Gertz, Morie A.

AU - Lacy, Martha Q.

AU - Geyer, Susan M.

AU - Fitch, Tom R.

AU - Fenton, Robert G.

AU - Fonseca, Rafael

AU - Isham, Crescent R.

AU - Ziesmer, Steven C.

AU - Erlichman, Charles

AU - Bible, Keith C.

PY - 2006/3

Y1 - 2006/3

N2 - 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.

AB - 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.

KW - Clinical trial

KW - Mcl-1

KW - Therapy

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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