DFMO: Targeted risk reduction therapy for colorectal neoplasia

Christina M. Laukaitis; Eugene W. Gerner

doi:10.1016/j.bpg.2011.09.007

DFMO: Targeted risk reduction therapy for colorectal neoplasia

Christina M. Laukaitis, Eugene W. Gerner

Medicine

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Strategies to decrease intracellular polyamine levels have been studied for their efficacy in reducing colorectal cancer (CRC) risk. A successful strategy combined agents that decreased polyamine synthesis by inhibiting ornithine decarboxylase with difluoromethylornithine (DFMO), and increased cellular export of polyamines by activating the spermidine/spermine acetyl transferase with non-steroidal anti-inflammatory drugs (NSAIDs). A Phase III trial treating resected adenoma patients with DFMO plus sulindac demonstrated marked reduction of metachronous adenomas, advanced adenomas and multiple adenomas compared to placebo. This combination regimen was well-tolerated, however there was a non-significant excess of cardiovascular events in the treatment arm compared to placebo as well as modest ototoxicity. Targeting this therapy to people at elevated risk of CRC, and employing clinical and genetic predictors, should improve patient benefit and reduce the risk of side effects to improve the acceptability of this strategy.

Original language	English (US)
Pages (from-to)	495-506
Number of pages	12
Journal	Best Practice and Research: Clinical Gastroenterology
Volume	25
Issue number	4-5
DOIs	https://doi.org/10.1016/j.bpg.2011.09.007
State	Published - Aug 2011

Keywords

Chemoprevention
Colorectal cancer
DFMO
Polyamines

ASJC Scopus subject areas

Gastroenterology

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10.1016/j.bpg.2011.09.007

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title = "DFMO: Targeted risk reduction therapy for colorectal neoplasia",

abstract = "Strategies to decrease intracellular polyamine levels have been studied for their efficacy in reducing colorectal cancer (CRC) risk. A successful strategy combined agents that decreased polyamine synthesis by inhibiting ornithine decarboxylase with difluoromethylornithine (DFMO), and increased cellular export of polyamines by activating the spermidine/spermine acetyl transferase with non-steroidal anti-inflammatory drugs (NSAIDs). A Phase III trial treating resected adenoma patients with DFMO plus sulindac demonstrated marked reduction of metachronous adenomas, advanced adenomas and multiple adenomas compared to placebo. This combination regimen was well-tolerated, however there was a non-significant excess of cardiovascular events in the treatment arm compared to placebo as well as modest ototoxicity. Targeting this therapy to people at elevated risk of CRC, and employing clinical and genetic predictors, should improve patient benefit and reduce the risk of side effects to improve the acceptability of this strategy.",

keywords = "Chemoprevention, Colorectal cancer, DFMO, Polyamines",

author = "Laukaitis, {Christina M.} and Gerner, {Eugene W.}",

note = "Funding Information: Role of the funding source Work described in this review was supported by grants from the National Institutes of Health to EWG and colleagues, including CA047396 , CA059024 , CN075019 , CA072008 , CA088078 , CA095960 and CA123065 . CML was also supported by CA023074 . ",

year = "2011",

month = aug,

doi = "10.1016/j.bpg.2011.09.007",

language = "English (US)",

volume = "25",

pages = "495--506",

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AU - Laukaitis, Christina M.

AU - Gerner, Eugene W.

N1 - Funding Information: Role of the funding source Work described in this review was supported by grants from the National Institutes of Health to EWG and colleagues, including CA047396 , CA059024 , CN075019 , CA072008 , CA088078 , CA095960 and CA123065 . CML was also supported by CA023074 .

PY - 2011/8

Y1 - 2011/8

N2 - Strategies to decrease intracellular polyamine levels have been studied for their efficacy in reducing colorectal cancer (CRC) risk. A successful strategy combined agents that decreased polyamine synthesis by inhibiting ornithine decarboxylase with difluoromethylornithine (DFMO), and increased cellular export of polyamines by activating the spermidine/spermine acetyl transferase with non-steroidal anti-inflammatory drugs (NSAIDs). A Phase III trial treating resected adenoma patients with DFMO plus sulindac demonstrated marked reduction of metachronous adenomas, advanced adenomas and multiple adenomas compared to placebo. This combination regimen was well-tolerated, however there was a non-significant excess of cardiovascular events in the treatment arm compared to placebo as well as modest ototoxicity. Targeting this therapy to people at elevated risk of CRC, and employing clinical and genetic predictors, should improve patient benefit and reduce the risk of side effects to improve the acceptability of this strategy.

AB - Strategies to decrease intracellular polyamine levels have been studied for their efficacy in reducing colorectal cancer (CRC) risk. A successful strategy combined agents that decreased polyamine synthesis by inhibiting ornithine decarboxylase with difluoromethylornithine (DFMO), and increased cellular export of polyamines by activating the spermidine/spermine acetyl transferase with non-steroidal anti-inflammatory drugs (NSAIDs). A Phase III trial treating resected adenoma patients with DFMO plus sulindac demonstrated marked reduction of metachronous adenomas, advanced adenomas and multiple adenomas compared to placebo. This combination regimen was well-tolerated, however there was a non-significant excess of cardiovascular events in the treatment arm compared to placebo as well as modest ototoxicity. Targeting this therapy to people at elevated risk of CRC, and employing clinical and genetic predictors, should improve patient benefit and reduce the risk of side effects to improve the acceptability of this strategy.

KW - Chemoprevention

KW - Colorectal cancer

KW - DFMO

KW - Polyamines

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DFMO: Targeted risk reduction therapy for colorectal neoplasia

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Keywords

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