dacarbazine (DTIC)

Indications

• malignant melanoma
• neuroblastoma
• soft tissue sarcomas
• refractory Hodgkin's lymphoma (used in ABVD regimen)
• islet cell tumor

Dosage

• 375 mg/m2 IV on days 1 & 15 on the month
• 50-250 mg/m2/day for 5 days; repeat every 3 weeks
• 75-125 mg/m2/day for 10 days; repeat every 4 weeks

Injection: 100 mg, 200 mg.

Pharmacokinetics

• activated by hepatic microsomal oxidases
• 10-15% penetrates CSF
• eliminated in the urine
• 1/2life is 5 hours

elimination via kidney

1/2life = 5 hours

Monitor

• signs of extravasation during IV administration
• complete blood count (CBC)

Adverse effects

(worse with consecutive doses)

• common (> 10%)
  • nausea/vomiting (moderate to severe)
  • diarrhea
  • myelosuppression
    • dose related
    • onset: 7 days; nadir 10-14 days; recovery 21-28 days
    • leukopenia (mild)
    • thrombocytopenia (mild) may be delayed 2-3 weeks
• less common (1-10%)
  • facial flushing, paresthesias, alopecia, rash, anorexia, metallic taste, flu-like syndrome
• uncommon (< 1%)
  • anaphylaxis, hepatotoxicity, stomatitis, photosensitivity,
• other
  • phlebitis
  • neurotoxicity
  • tissue necrosis after extravasation
  • orthostatic hypotension

• drug adverse effects of alkylating agents

Drug interactions

• phenytoin, phenobarbital, rifampin may increase metabolism of dacarbazine

Test interactions

increases serum K+

Mechanism of action

• alkylating agent
• vesicant

More general terms

• alkylating agent triazene

Component of

• brentuximab vedotin/doxorubicin/vinblastine/dacarbazine (A+AVD)
• doxorubicin (Adriamycin)/bleomycin/vinblastine/dacarbazine (ABVD)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2942
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5281007