Related Experiment Videos
Phase I study of mitonafide in solid tumors
M Llombart1, A Poveda, E Forner
1Instituto Valenciano de Oncologia (IVO), Spain.
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.
Insights
Mitonafide, a novel 3-nitronaphthalimide, showed dose-limiting central nervous system toxicity, including irreversible memory loss, in a phase I trial. Further studies with short intravenous infusions are not recommended due to this toxicity.
Area of Science:
- Oncology
- Pharmacology
- Toxicology
Background:
- Mitonafide is a novel 3-nitronaphthalimide derivative.
- It exhibits DNA intercalative properties, suggesting potential anticancer activity.
Purpose of the Study:
- To evaluate the safety and tolerability of mitonafide in a phase I clinical trial.
- To determine the dose-limiting toxicity of mitonafide administered via short intravenous infusions.
Main Methods:
- A phase I dose-escalation study was conducted.
- Thirty patients received mitonafide daily for 5 days every 21 days via short (1-hour) intravenous infusions.
- Doses ranged from 15.4 mg/m²/day to 138.6 mg/m²/day.
Main Results:
- The study was halted due to central nervous system (CNS) toxicity in 5 patients at doses above 118 mg/m²/day.
- All affected patients experienced irreversible memory loss.
- Three patients progressed to disorientation and confusion, with one developing dementia.
Conclusions:
- Short intravenous infusions of mitonafide are associated with dose-limiting CNS toxicity, specifically irreversible memory loss.
- This administration schedule is not recommended for future studies.
- Alternative administration schedules are being investigated in ongoing phase I trials.