Phase I study of mitonafide in solid tumors.
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.
Llombart
M
M
Instituto Valenciano de Oncologia (IVO), Spain.
Poveda
A
A
Forner
E
E
Fernández-Martos
C
C
Gaspar
C
C
Muñoz
M
M
Olmos
T
T
Ruiz
A
A
Soriano
V
V
Benavides
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007094:Imides; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D008875:Middle Aged; D053644:Naphthalimides; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; C019215:mitonafide