Mitomycin C undergoes reduction of its quinone function to generate a bifunctional DNA alkylating agent. It is a broadly active antineoplastic agent with a number of unpredictable toxicities, including delayed bronchospasm 12–14 h after dosing and a chronic pulmonary fibrosis syndrome more frequent at doses of 50–60 mg/m2. Cardiomyopathy has been described, particularly in a setting of prior radiation therapy. A hemolytic/uremic syndrome carries an ultimate mortality rate of 25–50% and is poorly treated by conventional component support and exchange transfusion. Mitomycin is a notable vesicant and causes substantial nausea and vomiting. It can be used for intravesical instillation. | Chapter 081. Principles of Cancer Treatment Part 14 Mitomycin C undergoes reduction of its quinone function to generate a bifunctional DNA alkylating agent. It is a broadly active antineoplastic agent with a number of unpredictable toxicities including delayed bronchospasm 12-14 h after dosing and a chronic pulmonary fibrosis syndrome more frequent at doses of 50-60 mg m2. Cardiomyopathy has been described particularly in a setting of prior radiation therapy. A hemolytic uremic syndrome carries an ultimate mortality rate of 25-50 and is poorly treated by conventional component support and exchange transfusion. Mitomycin is a notable vesicant and causes substantial nausea and vomiting. It can be used for intravesical instillation for curative treatment of superficial transitional bladder carcinomas and with radiation therapy for curative treatment of anal carcinoma. Mitoxantrone is a synthetic compound that was designed to recapitulate features of doxorubicin but with less cardiotoxicity. It is quantitatively less cardiotoxic comparing the ratio of cardiotoxic to therapeutically effective doses but is still associated with a 10 incidence of cardiotoxicity at cumulative doses of 150 mg m2. It also causes alopecia. Cases of acute promyelocytic leukemia APL have arisen shortly after exposure of patients to mitoxantrone particularly in the adjuvant treatment of breast cancer. While chemotherapy-associated leukemia is generally of the acute myeloid type APL arising in the setting of prior mitoxantrone treatment had the typical t 15 17 chromosome translocation associated with APL but the breakpoints of the translocation appeared to be at topoisomerase II sites that would be preferred sites of mitoxantrone action clearly linking the action of the drug to the generation of the leukemia. Etoposide was synthetically derived from the plant product podophyllotoxin it binds directly to topoisomerase II and DNA in a reversible ternary complex. It stabilizes the covalent .
