Dactinomycin (Actinomycin D) Mechanism intercalate between strands of DNA Clinical use Wilms' tumor Ewing's sarcoma rhabdomyosarcoma childhood tumors Toxicity myelosuppression Doxorubicin (Adriamycin) and Daunorubicin Mechanism intercalate between strands of DNA noncovalent breaks DNA → decreased replication free radical generation inhibit topoisomerase Clinical use Hodgkin's lymphomas part of the ABVD combination regimen Adriamycin Bleomycin Vinblastine Dacarbazine solid tumors breast, endometrial, ovary, and lung myelomas sarcomas Toxicity cardiotoxicity dilated cardiomyopathy dexrazoxane used to prevent cardiotoxicity iron chelating agent prevents formation of free radicals does not "trap" free radicals myelosuppression alopecia tissue damage if extravasates into extravascular space Bleomycin Mechanism free radical generation complexes with Fe and O2 breaks DNA → decreased replication G2-phase specific Clinical use Hodgkin's lymphoma part of ABVD regimen for Hodgkin's testicular cancer head and neck cancer skin cancer Toxicity pulmonary fibrosis pneumonitis skin changes myelosuppression is relatively insignificant Etoposide (VP-16) and Teniposide Mechanism inhibits DNA topoisomerase II (think eTWOposide) breaks DNA → decreased replication late S- to G2-phase specific Clinical use small cell carcinoma lung prostate testicular carcinoma Toxicity myelosuppression GI upset alopecia Irinotecan and Topotecan Mechanism inhibits DNA topoisomerase I (think 1rinotecan) prevents DNA replication by inhibiting DNA unwinding Clinical use colon, ovarian, and small cell lung cancer Toxicity myelosuppression diarrhea