Mitomycin C MMC

MMC is active against a range of solid tumours but is also used as a radio-sensitizer in chemo-irradiation.

MMC is inactive in its natural form and requires reduction before binding to DNA by alkylation to form adducts. This bioreductive activation may occur preferentially under the anaerobic conditions that are known to exist within some solid tumours.

Causes of resistance have not been well defined, but as a naturally occuring compound it appears to be a substrate for Pgp.

MMC is used in combination with other cytotoxics to treat breast cancer, non-small-cell lung cancer, and GI cancer. It is used as a radio-sensitizer in the treatment of anal cancer. MMC is effective in reducing recurrence of superficial bladder cancer where it is given intravesically, effectively eliminating systemic exposure to the drug.

The most important toxicity of MMC is myelosuppression, especially thrombocytopaenia, which is delayed and can be cumulative. Accordingly, MMC is given systemically every 6 weeks in contrast to the 3-weekly schedules usually used for other anti-tumour antibiotics.

Haemolytic-uraemic syndrome, pulmonary fibrosis and, cardiac complications are all uncommon, especially at low cumulative doses, but are potentially fatal. Other toxicities such as nausea and vomiting, alopecia, and stomatitis are usually mild, but extravasation can be serious.

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