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Synergistic action of high‐dose hydroxyurea when used with cyglophosphamide and certain new organoplatinum complexes in treatment of advanced L1210 leukemia
Author(s) -
Gale Glen R.,
Atkins Loretta M.,
Meischen Sandra J.,
Schwartz Paul
Publication year - 1978
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(197804)41:4<1230::aid-cncr2820410402>3.0.co;2-q
Subject(s) - medicine , cyclophosphamide , regimen , leukemia , pharmacology , chemotherapy , immunology
Seven new organoplatinum (Pt) compounds, cyclophosphamide (CY), and hydroxyurea (HU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 × DBA/2 mice. In each experiment the Pt + CY combination was supra‐additive, as has been shown with other Pt compounds when used with CY. HU at the dose used (1000 mg/kg) was only minimally effective when used alone. However, six of the seven Pt + CY + HU combination regimens enhanced markedly the increased life span of treated mice when compared with the corresponding dual Pt + CY combination. The triple drug regimen yielded cure rates (>60‐day survival) up to 70% in individual experiments. Collectively, the cure rate was 11% with the various Pt + CY combinations, and was increased to 53% upon inclusion of HU in the regimen. It is suggested that HU may inhibit a process whereby potentially lethal DNA damage produced by Pt + CY would otherwise be repaired. A reduced efficacy of HU when used at a single, high‐dose level was also noted, and a possible mechanism and potential significance of this observation are discussed.