DNA Intercalating Agents (antitumor antibiotics)

Question 1

Dactinomycin

Answer 1

Class: N/A

Mechanism of action: intercalates between G-C base pairs forming a complex that interferes with RNA pol (transcription). Also causes single strand DNA breaks.

Therapeutic uses: pediatric tumors (Wilms’ tumor, rhabdomyosarcoma, and Ewing’s sarcoma)
choriocarcinoma

Toxicity:
anorexia, nausea, vomiting
SEVERE MYELOSUPPRESSION: PANCYTOPEN

Question 2

Daunorubicin

Answer 2

Class: Anthracycline

Mechanism of action: Intercalate between DNA base pairs and donate electrons to form superoxide which then converts to H2O2 which in the presence of iron forms hydroxyl radical that cleaves DNA.

Therapeutic uses: AML

Toxicity: IRREVERSIBLE DOSE-LIMITING CARDIOTOXICITY (CARDIOMYOPATHY) AND ALOPECIA
Myelosuppression (neutopenia)
Stomatitis, GI disturbances

Other: Dexrazoxane (iron chelating agent) protects cardiovasculature

Question 3

Idarubicin

Answer 3

Class: Anthracycline

Mechanism of action: Intercalate between DNA base pairs and donate electrons to form superoxide which then converts to H2O2 which in the presence of iron forms hydroxyl radical that cleaves DNA.

Therapeutic uses: AML

Toxicity: IRREVERSIBLE DOSE-LIMITING CARDIOTOXICITY (CARDIOMYOPATHY) AND ALOPECIA
Myelosuppression (neutopenia)
Stomatitis, GI disturbances

Other: Dexrazoxane (iron chelating agent) protects cardiovasculature

Question 4

Doxorubicin

Answer 4

Class: Anthracycline

Mechanism of action: Intercalate between DNA base pairs and donate electrons to form superoxide which then converts to H2O2 which in the presence of iron forms hydroxyl radical that cleaves DNA.

Therapeutic uses: Sarcomas, Breast, Lung, Lymphomas (Hodgkin’s)

Toxicity: IRREVERSIBLE DOSE-LIMITING CARDIOTOXICITY (CARDIOMYOPATHY) AND ALOPECIA
Myelosuppression (neutopenia)
Stomatitis, GI disturbances

Other: Dexrazoxane (iron chelating agent) protects cardiovasculature

Question 5

Epirubicin

Answer 5

Class: Anthracycline

Mechanism of action: Intercalate between DNA base pairs and donate electrons to form superoxide which then converts to H2O2 which in the presence of iron forms hydroxyl radical that cleaves DNA.

Therapeutic uses: Breast (metastatic) and gastric

Toxicity: IRREVERSIBLE DOSE-LIMITING CARDIOTOXICITY (CARDIOMYOPATHY) AND ALOPECIA
Myelosuppression (neutopenia)
Stomatitis, GI disturbances

Other: Dexrazoxane (iron chelating agent) protects cardiovasculature

Question 6

Bleomycin

Answer 6

Class: N/A

Mechanism of Action: Bleomycin is a mixture of two copper-chelating peptides obtained from Streptomyces. In presence of iron and oxygen, bleomycin will form free radicals that induce ss and dsDNA breaks. Acts only in G2 phase.

Therapeutic uses: testicular, squamous cell carcinomas, lymphomas (Hodgkin’s)

Toxicity: PULMONARY TOXICITY (FIBROSIS)
CUTANEOUS TOXICITY (HYPERPIGMENTATION, HYPERKERATOSIS, ERYTHEMA)
Hyperthermia, headache, nausea, vomiting
Minimally immunosuppressive