Phase I study of mitonafide in solid tumors.

Abstract

Mitonafide was the first synthetized compound of a new series of 3-nitronaphthalimides with intercalative properties. A phase I study with a conventional escalation scheme was developed. The schedule of drug administration was a daily x 5 days by short (1 h) intravenous (i.v.) infusion, every 21 days. Thirty evaluable patients were treated at doses from 15.4 mg/m2/d x 5 days to 138.6 mg/m2/d x 5 days. The study was interrupted due to appearance of central nervous system toxicity in 5 patients treated at doses above 118 mg/m2 x 5 days. This toxicity consisted firstly of loss of memory in all patients. It was irreversible and progressed in 3 patients to disorientation and confusion, leading to dementia in one of them. This was considered to be dose-limiting toxicity, and since it appeared to be related to the administration schedule, no further studies with short i.v. infusions of mitonafide are recommended. A phase I study utilizing a more desirable administration schedule over longer periods of time is ongoing in other centers.

• Authors: M Llombart, A Poveda, E Forner, C Fernández-Martos, C Gaspar, M Muñoz, T Olmos, A Ruiz, V Soriano, A Benavides
• Journal: Investigational new drugs (Invest New Drugs) Vol. 10 Issue 3 Pg. 177-81 (Aug 1992) ISSN: 0167-6997 [Print] United States
• PMID: 1428727 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Antineoplastic Agents
• Imides
• Isoquinolines
• Naphthalimides
• mitonafide

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Female
• Humans
• Imides
• Infusions, Intravenous
• Isoquinolines (administration & dosage, adverse effects)
• Male
• Memory Disorders (chemically induced)
• Middle Aged
• Naphthalimides
• Neoplasms (drug therapy)