- Antitumor antibiotic (cytotoxic)
- Derived from Streptomyces species
Mechanism of Action
- Intercalates into DNA at the transcription initiation complex
- Inhibits RNA synthesis (mainly mRNA transcription)
- Leads to cell cycle arrest and apoptosis, preferentially affecting rapidly dividing cells
Indications (Pediatric & Adult)
- Pediatric tumors:
- Wilms tumor (nephroblastoma)
- Rhabdomyosarcoma
- Ewing sarcoma (occasionally in combination regimens)
- Hepatoblastoma
- Other: Gestational trophoblastic disease
- Route: IV (central or peripheral, slow infusion)
- Distribution: Widely distributed; minimal CNS penetration
- Metabolism: Hepatic
- Excretion: Biliary/fecal (mainly)
Dosing (Pediatric Example)
- Wilms tumor: 0.045–0.05 mg/kg IV every 3–4 weeks in combination therapy
- Often combined with vincristine ± doxorubicin depending on risk stratification
Adverse Effects / Toxicities
- Myelosuppression: neutropenia, thrombocytopenia, anemia
- Hepatotoxicity: elevated transaminases, cholestasis
- Mucositis / stomatitis
- Nausea / vomiting
- Rare: veno-occlusive disease in high-risk regimens
Pharmacist Considerations
- Preparation / administration:
- Handle as cytotoxic agent with PPE
- Slow IV infusion to reduce local toxicity
- Monitoring:
- CBC (myelosuppression)
- LFTs (hepatic function)
- Hydration to support clearance if combined with nephrotoxic agents
- Drug interactions:
- Combination with other myelosuppressive chemo → additive bone marrow toxicity
High-Yield BPS Pearls
- Acts primarily on rapidly dividing embryonal cells → cornerstone in pediatric solid tumors
- Main toxicities: myelosuppression, hepatotoxicity, mucositis
- Often used in combination regimens:
- Wilms tumor: Vincristine + Actinomycin D ± Doxorubicin
- Rhabdomyosarcoma: VAC regimen (Vincristine, Actinomycin D, Cyclophosphamide)
Synonyms
Dactinomycin