𝔖 Bobbio Scriptorium
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Phase I evaluation of intravenous difluoromethylornithine — a polyamine inhibitor

✍ Scribed by A. M. Maddox; M. J. Keating; K. E. McCredie; E. Estey; E. J. Freireich

Publisher
Springer US
Year
1985
Tongue
English
Weight
411 KB
Volume
3
Category
Article
ISSN
0167-6997

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✦ Synopsis

Difluoromethylornithine (DFMO), a non-competitive inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of the polyamine synthetic pathway was evaluated in a Phase I trial. Intravenous DFMO was given to twenty patients with refractory leukemia by continuous infusion in doses from 5.5 to 64 g/m 2. Toxicity clearly attributable to the drug was not severe and other than nausea and vomiting did not increase with dose. The previously reported ototoxicity which occurred with the oral form appeared to be less frequent. Loss of hearing which improved when the drug was stopped was seen in four patients, three of whom were simultaneously receiving aminoglycosides. Anorexia occurred in some patients at all doses. Vomiting, necessitating dosage reduction, was a significant problem at the highest dose administered. No patient achieved a remission but there was stabilization or decrease in circulating blast cells in several patients. This growth inhibition did not appear to be dosage related.

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