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Dacarbazine, cisplatin, carmustine for melanoma

Posted Jun 18 2010 1:16am

Metastatic melanoma responds poorly to chemotherapy with the main drugs being temozolomide or dacarbazine after failure of immunotherapy or vaccination. A randomized study suggests that cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, recently a phase III trial was performed with patients randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. The authors concluded that "although BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma."

Another comparative study was of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. The overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival. A study of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) against a chemoimmunotherapy regimen revelaed no difference.

However NCCN lists both dacarbazine based therapy and biochemotherapy (p.16) as an option.

Atzpodien J, Neuber K, Kamanabrou D, Fluck M, Bröcker EB, Neumann C, Rünger TM, Schuler G, von den Driesch P, Müller I, Paul E, Patzelt T, Reitz M.Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM).Br J Cancer. 2002 Jan 21;86(2):179-84.

Chiarion Sileni V, Nortilli R, Aversa SM, Paccagnella A, Medici M, Corti L, Favaretto AG, Cetto GL, Monfardini S. Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients.
Melanoma Res. 2001 Apr;11(2):189-96.

A. A. Trinh
Current management of metastatic melanoma
Am. J. Health Syst. Pharm., December 15, 2008; 65(24_Supplement_9): S3 - S8.

Maja A. Hofmann , Wolfram Sterry , and Uwe Trefzer
Complex Combination Biochemotherapy Regimen in Advanced Metastatic Melanoma in a Non-intensive Care Unit: Toxicity or Benefit?
Jpn. J. Clin. Oncol. 37: 224-229.

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