Phase I trial of α-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) in patients with advanced prostatic cancer Journal Article

  

Authors:	Herr, H. W.; Warrel, R. P.; Burchenal, J. H.
Article Title:	Phase I trial of α-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) in patients with advanced prostatic cancer
Abstract:	Both α-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells and DFMO combined with MGBG has shown synergistic cytotoxicity in an experimental prostatic tumor, we evaluated these agents in phase I clinical trial involving 5 patients with advanced, hormone-resistant prostatic cancer. Toxic reaction to combined DFMO and MGBG was dose-related and included nausea, fatigue, and diarrhea especially with the higher doses of MGBG. No therapeutic responses of significance were seen, but toxicity precluded adequate evaluation. Future Phase II studies of combined DFMO and MGBG should employ low, nontoxic doses of MGBG combined with evaluation of polyamine levels and inhibition of polyamine enzymatic activity to minimize toxicity. © 1985.
Keywords:	cancer chemotherapy; fatigue; case report; advanced cancer; diarrhea; drug efficacy; adenocarcinoma; nausea; antineoplastic combined chemotherapy protocols; dose-response relationship, drug; prostatic neoplasms; gastrointestinal toxicity; eflornithine; drug dose; phase 1 clinical trial; drug therapy; adverse drug reaction; therapy; intravenous drug administration; prostate carcinoma; mitoguazone; oral drug administration; drug evaluation; intoxication; male genital system; human; male; priority journal; amidinohydrazone; polyamine biosynthesis
Journal Title:	Urology
Volume:	28
Issue:	6
ISSN:	0090-4295
Publisher:	Elsevier Science, Inc.
Date Published:	1986-12-01
Start Page:	508
End Page:	511
Language:	English
DOI:	10.1016/0090-4295(86)90154-8
PUBMED:	3097903
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0022965395&doi=10.1016%2f0090-4295%2886%2990154-8&partnerID=40&md5=c10e2f28cb7050b9266729d6e5cc9641
Notes:	Article -- Export Date: 18 August 2021 -- Source: Scopus

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