Antitumor antibiotics

Question 1

Dactinomycin (actinomycin D)

Answer 1

Mechanism: Intercalates in DNA.

Clinical use: Wilms’ tumor, Ewing’s sarcoma, rhabdomyosarcoma. Used for childhood tumors (“children act out”).

Toxicity: Myelosuppression.

Question 2

Dexorubicin (Adriamycin), daunorubicin

Answer 2

Mechanism: Generate free radicals.
Noncovalently intercalate in DNA -> breaks in DNA -> decreased replication.

Clinical use: Solid tumors, leukemias, lymphomas.

Toxicity: Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Toxic to tissues following extravasation.
Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity.

Question 3

Bleomycin

Answer 3

Mechanism: Induces free radical formation, which causes breaks in DNA strands.

Clinical use: Testicular cancer, Hodgkin’s lymphoma.

Toxicity: Pulmonary fibrosis, skin changes. Minimal myelosuppression.