Dactinomycin

Dactinomycin (actinomycin D, Cosmegen) is one of a family of chromopeptides produced by Streptomyces. It is known to bind noncovalently to double-strand DNA by partial intercalation, inhibiting DNA-directed RNA synthesis. The drug is most toxic to proliferating cells, but it is not specific for any one phase of the cell cycle. Resistance to dactinomycin is caused by decreased ability of tumor cells to take up and retain the drug, and it is associated with cross-resistance to vinca alkaloids, the anthracyclines, and certain other agents (multidrug resistance).

Dactinomycin is cleared rapidly from plasma, does not enter the brain, is not appreciably metabolized or protein bound, and is gradually excreted in both bile and urine. Virtually no drug is detected in CSF.

Dactinomycin is used in curative combined treatment of Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma, and gestational choriocarcinoma. It is active in testicular tumors, lymphomas, melanomas, and sarcomas, although its use in most of these malignancies has been supplanted by other agents.

The major side effects of dactinomycin are severe nausea, vomiting, and myelosuppression. Mucositis, diarrhea, alopecia, and radiation recall reactions may occur. The drug is immunosuppressive and carcinogenic.

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