Dactinomycin

Summary

Dactinomycin (Actinomycin D) is a cytotoxic chromopeptide antibiotic derived from Streptomyces parvullus. It is one of the oldest antineoplastic agents and is used in combination chemotherapy regimens for several pediatric and adult malignancies including Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, gestational trophoblastic neoplasia, and testicular carcinoma.

Mechanism of Action

Intercalates into double-stranded DNA by inserting between adjacent guanine-cytosine base pairs, inhibiting DNA-dependent RNA polymerase and thereby blocking transcription. Also causes single- and double-strand DNA breaks at high concentrations.

Routes of Administration

Goals & Uses

• Wilms tumor treatmentOncologyHigh
• Gestational trophoblastic neoplasiaOncologyHigh
• Rhabdomyosarcoma treatmentOncologyHigh
• Testicular carcinoma treatmentOncologyModerate
• Ewing sarcoma treatmentOncologyHigh
• Regional perfusion for solid tumorsOncologyModerate

Contraindications

• Chickenpox (varicella) or herpes zoster infectionInfectionHigh
• Recent live vaccinesImmunologicalModerate
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Severe bone marrow suppressionHematologicHigh
• Hepatic veno-occlusive disease (in combination with radiation)HepatotoxicityHigh

Adverse Effects

• AlopeciaDermatologicCommonHair loss
• Mucositis / stomatitisGastrointestinalCommon
• Nausea and vomitingGastrointestinalCommon
• Tissue necrosis (extravasation)Local/dermatologicalUncommon
• MyelosuppressionHematologicCommon
• Hepatotoxicity / veno-occlusive diseaseHepaticUncommon

Drug Interactions

• Live vaccinesHigh
• Radiation therapyHigh
• Other myelosuppressive agentsModerate
• Vitamin K antagonists (warfarin)Moderate

Population Constraints

• Infants < 6 monthsPediatricRelative
• Breastfeeding womenReproductiveAbsolute
• Patients with hepatic impairmentOrgan FunctionRelative
• Elderly patientsAgeRelative
• Pregnant womenReproductiveAbsolute

Regulatory Status

• European UnionApprovedApproved: Wilms tumor, Rhabdomyosarcoma, Gestational trophoblastic neoplasia, Ewing sarcomaApproved in EU member states; available through national marketing authorizations.
• United StatesApprovedApproved: Wilms tumor, Rhabdomyosarcoma, Ewing sarcoma, Gestational trophoblastic neoplasia, Testicular carcinoma, Regional perfusion for locally recurrent or locoregional solid malignanciesFDA-approved; marketed as Cosmegen by Recordati Rare Diseases. Orphan drug designation for certain indications.
• United KingdomApprovedApproved: Wilms tumor, Rhabdomyosarcoma, Gestational trophoblastic neoplasiaLicensed in the UK; included in NHS cancer treatment protocols.

FDA-approved. Designated as an orphan drug for certain indications. Classified as a vesicant; extravasation can cause severe tissue damage. Pregnancy Category D (teratogenic and embryotoxic).

Evidence & Sources

No sources recorded yet.