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Bending the Curve Trial by Trial
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Nitrosoureas, triazenes, alkyl sulfonates, aziridines and related alkylatorsIn useSyntheticNeeds review

Dacarbazine

Also known as DTIC, DTIC-Dome, NSC-45388

An intravenous triazene. A current US label lists metastatic malignant melanoma and, as second-line therapy with other agents, Hodgkin lymphoma. A 2004 review described single-dose dacarbazine as the reference regimen in advanced melanoma.

From discovery to approval

  1. 1961 or later · No earlier than

    A 1982 lecture by J. A. Montgomery says Southern Research Institute developed two classes of anticancer agents, the nitrosoureas and the imidazole triazines. Shealy and colleagues reported the diazo compound 5-diazoimidazole-4-carboxamide in 1961. No paper naming dacarbazine was found, so 1961 is a lower bound. A 1962 paper from the group is titled Antitumor activity of triazenoimidazoles.[2][3][4][5]

  2. 1975-05-27 · FDA regular · 14 years after first description

    Dacarbazine for injection (DTIC-Dome), NDA 017575, original approval, classed as a new molecular entity with standard review in the Drugs@FDA history. The original label is not available there, so the indication at approval is not stated here; a current label lists metastatic malignant melanoma and Hodgkin disease as second-line therapy with other agents. The type regular is an inference: no accelerated-approval wording was found.[6]

How it works

Dacarbazine needs metabolic activation, which yields the methyltriazene MTIC, thought to be responsible for its antitumour activity. The US label says the exact mechanism is not known and lists three hypotheses: purine-analogue inhibition of DNA synthesis, alkylation, and interaction with SH groups.[1]

Where it came from and why

The sources read do not state the design aim. The 1961 and 1962 papers from the group are titled as syntheses of potential anticancer agents and as coupling reactions of the diazo compound. The 1961 year is that of the diazo precursor, not of dacarbazine.

Cancers

  • Metastatic malignant melanoma

    The US label lists metastatic malignant melanoma. A 1976 report from the Central Oncology Group describes DTIC as an effective drug in malignant melanoma, and a 1999 phase III trial of 240 patients compared it with the Dartmouth regimen.[7]

  • Hodgkin lymphoma

    The US label lists Hodgkin disease as second-line therapy in combination with other agents. A 1975 trial compared MOPP with a four-drug combination of adriamycin, bleomycin, vinblastine and imidazole carboxamide.[8]

Worth knowing

  • In a phase III trial of 240 patients with stage IV melanoma, the response rate was 10.2% with dacarbazine alone and 18.5% with the Dartmouth regimen (P = .09), with no difference in survival; the authors wrote that dacarbazine remains the reference standard treatment for stage IV melanoma.[9]
  • In a randomised phase III trial of 305 patients with advanced metastatic melanoma, median survival was 7.7 months with temozolomide and 6.4 months with dacarbazine (hazard ratio 1.18; 95% CI 0.92 to 1.52), and median progression-free survival was 1.9 and 1.5 months (P = .012).[10]
  • A 2004 review states that dacarbazine was approved for metastatic melanoma in the 1970s, that combining it with other drugs failed to give clinically meaningful survival improvements, and that single-dose schedules appear as effective as multiple-dose schedules.[11]
  • In vitro, temozolomide and MTIC were cytotoxic without liver microsomes, whereas dacarbazine required metabolic activation to generate MTIC.[1]
  • In the 1975 comparison of MOPP with ABVD in advanced Hodgkin disease, complete remission occurred in 76% with MOPP and 75% with ABVD among 45 evaluable patients, with no cross-resistance between the regimens.[8]

On this site

References

  1. Tsang LL, Quarterman CP, Gescher A, Slack JA. Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide. Cancer Chemother Pharmacol. 1991;27(5):342-6. PubMedDOI
  2. Montgomery JA. Has the well gone dry? The First Cain Memorial Award Lecture. Cancer Res. 1982;42(10):3911-7. PubMed
  3. Shealy YF, Struck RF, Holum LB, Montgomery JA. Synthesis of potential anticancer agents. XXIX. 5-Diazoimidazole-4-carboxamide and 5-diazo-v-triazole-4-carboxamide. J Org Chem. 1961;26(7):2396-401. DOI
  4. Shealy YF, Krauth CA, Montgomery JA. Imidazoles. I. Coupling reactions of 5-diazoimidazole-4-carboxamide. J Org Chem. 1962;27(6):2150-4. DOI
  5. SHEALY YF, MONTGOMERY JA, LASTER WR Jr. Antitumor activity of triazenoimidazoles. Biochem Pharmacol. 1962;11:674-6. PubMedDOI
  6. U.S. Food and Drug Administration. Drugs@FDA: NDA 017575, DTIC-DOME (dacarbazine), overview page, accessed 20 October 2026. Source
  7. Hikma Pharmaceuticals USA Inc. Dacarbazine for injection: prescribing information. DailyMed, set ID 0d81315c-7021-4091-b703-ad135390c936, published 29 September 2025. Source
  8. Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975;36(1):252-9. PubMedDOI
  9. Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, et al. Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol. 1999;17(9):2745-51. PubMedDOI
  10. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18(1):158-66. PubMedDOI
  11. Eggermont AM, Kirkwood JM. Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?. Eur J Cancer. 2004;40(12):1825-36. PubMedDOI
  12. Johnson RO, Metter G, Wilson W, Hill G, Krementz E. Phase I evaluation of DTIC (NSC-45388) and other studies in malignant melanoma in the Central Oncology Group. Cancer Treat Rep. 1976;60(2):183-7. PubMed