Dacarbazine

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Dacarbazine (5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC)) is an atypical alkylating chemotherapy drug used for treatment of certain canine neoplasms.

This drug is aqueous soluble, orally bioavailable and has been safely used in combination with temozolomide[1], carboplatin, cyclophosphamide[2], lomustine, vincristine and doxorubicin.

This drug has been used as a single agent for treatment of relapsed lymphoma (response rate approx. 35% with a median progression-free interval of 40 days)[3][4][5]. In relapsed lymphoma, it is sometimes used in combination with lomustine[6] or dactinomycin[7] for improved response rates.

Dacarbazine is also used in multidrug regimens such as DAV protocol (doxorubicin, dacarbazine and vincristine combination). With this protocol, doxorubicin and dacarbazine are administered on day 1 while vincristine is administered on days 8 and 15, repeated every 21 days for a maximum of six cycles or until disease progression. This regimen has shown efficacious (50% response rate; 125 day survival) for treatment of canine hemangiosarcoma[8].

Common side-effect is neutropenia.

Recommended dose rate in dogs is 800 - 1,000 mg/m2 every 2 - 3 weeks as a 4 - 5 hour IV infusion.

References

  1. Dervisis NG et al (2007) Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphoma. J Am Vet Med Assoc 231(4):563-569
  2. Penning TD et al (2009) Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J Med Chem 52(2):514-523
  3. Dervisis NG & Kitchell BE (2010) Dacarbazine as single-agent therapy for relapsed lymphoma in dogs. J Vet Intern Med 24(1):4
  4. Takeuchi Y et al (2010) Long term survival of primary skeletal muscle lymphoma in a miniature dachshund. J Vet Med Sci 72(5):673-677
  5. Griessmayr PC et al (2009) Dacarbazine as single-agent therapy for relapsed lymphoma in dogs. J Vet Intern Med 23(6):1227-1231
  6. Flory AB et al (2008) Combination of CCNU and DTIC chemotherapy for treatment of resistant lymphoma in dogs. J Vet Intern Med 22(1):164-171
  7. Dervisis NG et al (2007) Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphoma. J Am Vet Med Assoc 231(4):563-569
  8. Dervisis NG et al (2011) Treatment with DAV for advanced-stage hemangiosarcoma in dogs. J Am Anim Hosp Assoc 47(3):170-178