Journal of clinical pharmacy and therapeutics · 2010
The repositioning of the anti-fungal agent ciclopirox olamine as a novel therapeutic agent for the treatment of haematologic malignancy.
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Weir S J, Patton L, Castle K, Rajewski L, Kasper J, Schimmer A D
Аннотация
WHAT IS KNOWN AND OBJECTIVE: 6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone (ciclopirox) and specifically its olamine salt 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone 2-aminoethanol salt (ciclopirox olamine) are anti-fungal agents currently used for the treatment of mild to moderate cutaneous fungal infection. Our objective is to comment on the opportunity to rapidly reposition ciclopirox and its olamine for the treatment of haematologic malignancy by leveraging its prior published toxicology and pharmacology data.
COMMENT: Ciclopirox olamine chelates intracellular iron and displays preclinical efficacy in the treatment of haematologic malignancy. Currently, an ongoing study is evaluating topical ciclopirox olamine for the treatment of cervical cancer. Doses of ciclopirox olaine required for a systemic anti-cancer effect appear pharmacologically achievable. However, caution is required as at the highest doses tested in animal toxicology studies, irreversible cardiac degeneration was observed.
WHAT IS NEW AND CONCLUSION: The existing pharmacology and toxicology data suggest that systemic ciclopirox olamine could be repositioned as a new investigational anti-cancer agent. The available pharmacology and toxicology data should aid in the design of phase I clinical trials of this agent in patients with refractory haematologic malignancies.
COMMENT: Ciclopirox olamine chelates intracellular iron and displays preclinical efficacy in the treatment of haematologic malignancy. Currently, an ongoing study is evaluating topical ciclopirox olamine for the treatment of cervical cancer. Doses of ciclopirox olaine required for a systemic anti-cancer effect appear pharmacologically achievable. However, caution is required as at the highest doses tested in animal toxicology studies, irreversible cardiac degeneration was observed.
WHAT IS NEW AND CONCLUSION: The existing pharmacology and toxicology data suggest that systemic ciclopirox olamine could be repositioned as a new investigational anti-cancer agent. The available pharmacology and toxicology data should aid in the design of phase I clinical trials of this agent in patients with refractory haematologic malignancies.