Phase I study of mitonafide in solid tumors |
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Authors: | Manuel Llombart Andrés Poveda Ernesto Forner Carlos Fernández-Martos Cristóbal Gaspar Miguel Muñoz Teresa Olmos Amparo Ruiz Virtudes Soriano Ana Benavides Miguel Martin Erich Schlick Vicente Guillem |
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Affiliation: | (1) Instituto Valenciano de Oncología (IVO), Spain;(2) Laboratorios Knoll, SA, Spain;(3) Knoll AG, Germany |
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Abstract: | Summary 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 ×5 days by short (1h) intravenous (i.v.) infusion, every 21 days. Thirty evaluable patients were treated at doses from 15.4 mg/m2/d×5 days to 138.6 mg/m2/d×5 days. The study was interrupted due to appearance of central nervous system toxicity in 5 patients treated at doses above 118 mg/m2×5 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. |
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Keywords: | phase I mitonafide solid tumors |
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