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Glutamic acid modification of vincristine toxicity.

Glutamic acid modification of vincristine toxicity.

Authors :
Jackson DV Jr
Rosenbaum DL
Carlisle LJ
Long TR
Wells HB
Spurr CL
Source :
Cancer biochemistry biophysics [Cancer Biochem Biophys] 1984 Sep; Vol. 7 (3), pp. 245-52.
Publication Year :
1984

Abstract

The principal limiting feature of the antitumor agent, vincristine, in the clinic has been neurotoxicity; there are no known agents which can routinely prevent or decrease this side effect. Glutamic acid in laboratory and clinical investigations in the early 1960s was found to antagonize vinblastine, another clinically useful vinca alkaloid. Glutamic acid 250 mg/kg/d i.p. was given to normal mice treated with repetitive doses of vincristine 1.5 mg/kg every other day. When glutamic acid was given both before and during vincristine administration, it produced a 49-79% increase in survival compared to control mice receiving vincristine only (p less than 0.01). Other schedules of glutamic acid administration were ineffective. Also, there appeared to be a delay in development of neurotoxic manifestations (toe-walking gait) but the results were not as consistent as the improvement in survival. Glutamic acid given to tumor-bearing mice (P-388 and P-1534 murine leukemia) did not inhibit the antitumor effect of vincristine-induced host toxicity in a schedule-dependent fashion without inhibition of the antitumor effect of vincristine.

Details

Language :
English
ISSN :
0305-7232
Volume :
7
Issue :
3
Database :
MEDLINE
Journal :
Cancer biochemistry biophysics
Publication Type :
Academic Journal
Accession number :
6149015