Dacarbazine
Dacarbazine (often referred to as **DTIC**) is a parenteral **antineoplastic agent** primarily used in veterinary oncology for the treatment of relapsed lymphomas, soft tissue sarcomas, and melanomas in dogs. **Clinical Pearls:** * Dacarbazine is a **prodrug** that requires hepatic activation to exert its cytotoxic effects. * It is **not recommended for use in cats** because it is unknown if the feline liver can adequately metabolize it into its active form, making its efficacy and safety highly unpredictable in this species. * It is a severe **vesicant**; extravasation can cause profound tissue necrosis. It must be administered via a perfectly placed intravenous catheter, typically as a slow, diluted infusion.
Mechanism: Dacarbazine is a prodrug that undergoes hepatic N-demethylation (likely via **cytochrome P450** enzymes) to form an active intermediate, which then degrades to form **reactive carbonium ions**. * **Alkylating Activity:** These carbonium ions act as alkylating agents → cross-link DNA strands → interfere with DNA transcription and replication. * **Antimetabolite Activity:** It also inhibits the incorporation of purine nucleosides into DNA. * It possesses minimal immunosuppressant activity and is generally considered **cell cycle-phase nonspecific**.
Dosing by species
- Relapsed lymphoma, soft tissue sarcomas, melanoma · 800-1000 mg/m2 · IV · every 2-3 weeks · over 5-8 hours · NOT mg/kg. Depending on the protocol used.
- Relapsed Lymphoma (Rescue Protocol) · 800-1000 mg/m2 · IV · every 3 weeks · as determined by oncologist · Administer as a slow IV infusion (over several hours) to minimize adverse effects. Pre-medicate with antiemetics.
- Relapsed Lymphoma (Alternative schedule) · 200 mg/m2 · IV · sid · for 5 consecutive days · Repeat cycle every 3 weeks.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Cats (due to unknown hepatic metabolism capabilities)
- Patients with known hypersensitivity to the drug
- Pregnancy (teratogenic)
- Pre-existing severe myelosuppression
- Severe hepatic dysfunction
- Pregnancy and lactation
- Known hypersensitivity
Adverse effects
- Severe gastrointestinal toxicity (vomiting, anorexia, diarrhea) - often dose-limiting
- Bone marrow suppression (leukopenia, thrombocytopenia) - nadir occurs several weeks post-treatment
- Severe tissue damage and pain (if extravasated)
- Venous spasm and phlebitis during IV administration
- Alopecia (rare)
- Hepatotoxicity (rare)
- Renal impairment (rare)
- Photosensitivity (rare)
- Severe nausea and vomiting
- Myelosuppression (neutropenia, thrombocytopenia)
- Tissue necrosis if extravasated
- Hepatotoxicity
- Lethargy
- Anorexia
Drug interactions
- Myelosuppressive drugs (e.g., other antineoplastics, chloramphenicol, flucytosine, colchicine) · May cause additive myelosuppression when used concurrently with DTIC.
- Rifampin · May increase the hepatic metabolism of DTIC.
- Phenobarbital · May increase the hepatic metabolism of DTIC. · moderate
- Phenytoin · May increase the hepatic metabolism of DTIC.
- Other myelosuppressive agents · Additive bone marrow suppression · major
Monitoring
- Efficacy (tumor response)
- CBC with differential and platelets (monitor for myelosuppression)
- Renal function tests
- Hepatic function tests
- IV catheter site for signs of extravasation during infusion
- Complete Blood Count (CBC) prior to each dose and at nadir (typically 7-14 days post-treatment)
- Liver function tests (ALT, AST, Bilirubin)
- Renal function
- IV catheter site for signs of extravasation
- Gastrointestinal signs (vomiting, diarrhea)
Overdose
Because of the severe toxic potential of this agent, iatrogenic overdoses must be strictly avoided. Recheck all dosage calculations carefully (ensure dosing is based on body surface area in mg/m2, not mg/kg). Overdose will likely result in profound, life-threatening bone marrow suppression and severe gastrointestinal toxicity. Treatment is supportive.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.