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Synergistic action of two polyamine antimetabolites leads to a rapid therapeutic response in childhood leukemia
Author(s) -
Siimes M.,
Seppänen P.,
AlhonenHongisto L.,
Jänne J.
Publication year - 1981
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910280506
Subject(s) - methylglyoxal , ornithine , drug , leukemia , polyamine , pharmacology , chemistry , drug action , mechanism of action , asparaginase , cancer research , lomustine , medicine , biochemistry , lymphoblastic leukemia , chemotherapy , immunology , enzyme , vincristine , amino acid , arginine , in vitro , cyclophosphamide
Sequential administration of α‐difluoromethyl ornithine and methylglyoxal bis(guanylhydrazone), two differently acting inhibitors of the biosynthesis of natural polyamines, produced a rapid and distinct therapeutic response in four children with advanced lymphoblastic and in one with myeloblastic leukemia. The synergism between the action of the two compounds was based upon a unique drug interaction; a preceding treatment with difluoromethyl ornithine greatly increased the uptake of subsequently administered methylglyoxal bis‐(guanylhydrazone) as verified by the actual determinations of the latter drug in the circulating leukemia cells. The side‐effects associated with the combined drug regimen were either absent or mild.