A prospective study on the dose dependency of cardiotoxicity induced by mitomycin C

Since 1975 mitomycin C (MMC) has been suggested to be cardiotoxic, especially when combined with or given following doxorubicin. Data on dose dependency or incidence concerning this side effect were not known. We have initiated a prospective study to obtain some more data on these subjects. Forty-four MMC-treated patients were studied, 37 of them could be evaluated. All patients were studied by repeated physical examinations, chest X-rays, electro- and echocardiography and radionuclide left ventricular ejection fraction (EF) determinations. The results were evaluated per cumulative dose level. One of the patients developed cardiac failure after 30 mg m-2 MMC and only 150 mg m-2 doxorubicin. The cardiac failure was predicted by a drop in EF determined during a cold pressor test. None of the other patients developed clinical cardiotoxicity, nor did the studied parameters change. The literature on this subject was also reviewed. Based on the combined data from the present study and the literature, we suggest that MMC-related cardiotoxicity is dose dependent, occurring at cumulative dose levels of 30 mg m-2 or more, mainly in patients also (previously or simultaneously) treated with doxorubicin. The incidence is likely to be less than 10% even for this risk group.