Melanoma dacarbazine

Melanoma Dacarbazine, cisplatin, temozolomide Lomustine, hydroxyurea, mitomycin, dactinomycin, interferon, tamoxifen... 

Dacarbazine is the most active compound used for treating metastatic melanoma. It is also combined with anthracyclines and other cytostatics in the treatment of different sarcomas and Hodgkin s disease. Dacarbazine may cause severe nausea and vomiting. Myelosuppres-sion results in leukopenia and thrombocytopenia. Alopecia and transient abnormalities in renal and hepatic function also occur. 

While the exact mechanism of action remains unclear, dacarbazine appears to inhibit DNA, RNA, and protein synthesis. Dacarbazine disappears rapidly from the plasma, with a terminal half-life of about 40 minutes. Dacarbazine has shown clinical benefit in the treatment of melanoma, Hodgkin s lymphoma, and soft tissue sarcomas. Side effects include myelosuppression, severe nausea and vomiting, and a flulike syndrome that starts about 7 days after treatment and lasts 1 to 3 weeks. 

Arani RB, Soong S-1, Weiss HL, Wood Ml et al. (2001) Phase specific analysis of herpes zoster associated pain data a new statistical approach Statistics in Medicine, 20, 2429-2439 Bedikian AY, MiUward M, Pehamberger H, Conry R et al. (2006) Bcl-2 Antisense (obUmersen sodium) plus dacarbazine in patients with advanced melanoma The ObUmersen Melanoma Study Group Journal of Clinical Oncology, 24, 4738-4745 Bland M (2004) Cluster randomised trials in the medical Uterature two bibliometric surveys BMC Medical Research Methodology, 4, 21... 

Various antineoplastics altretamine amsacrine 1-asparaginase dacarbazine melanoma theraccine porfimer sodium procarbazine hydrochloride topotecan hydrochloride tretinoin (dil-trans retinoic acid), systemic... 

Legha, S.S., S. Ring, O. Eton, A. Bedikian, A.C. Buzaid, C. Plager, and N. Papadopon-los. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Chn Oncol, 1998.16(5) 1752-9. 

Falkson, C.I., J. Ibrahim, J.M. Kirkwood, A.S. Coates, M.B. Atkins, and R.H. Blnm, Phase HI trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma an Eastern Cooperative Oncology Group study. J Clin Oncol, 1998.16(5) 1743-51. 

Dacarbazine Methylates DNA and inhibits DNA synthesis and function Flodgkin s lymphoma, melanoma, soft tissue sarcoma Nausea and vomiting Myelosuppression, central nervous system toxicity with neuropathy, ataxia, lethargy, and confusion... 

Dacarbazine DTIC-Dome Malignant melanoma refractory Hodgkin s lymphomas Gl distress (nausea, vomiting, loss of appetite] blood disorders (leukopenia, thrombocytopenia]... 

Dacarbazine (DTIC-Dome) is metabolized to an active alkylating substance. It is used in the treatment of malignant melanoma and causes myelosuppression. 

P-Carotene has been shown to enhance the cytotoxicity of melphalan and BCNU on human squamous carcinoma cells and of cisplatin and dacarbazine on melanoma cells. In mice with transplanted mammary carcinoma, P-carotene enhanced the antitumor effect of cyclophosphamide, and in mice transplanted with Fsall fibrosarcoma or SCC VII carcinoma, p-carotene enhanced the antitumor effect of melphalan, BCNU, doxorubicin, and etoposide. p-Carotene (5 to 50 mg/kg) has been shown to reduce the genotoxicity of cyclophosphamide in mice and of mitomycin C, methyl methanesulfonate, and bleomycin in cultured cells. P-Carotene also reduced the rate of tumor induction in animals receiving chronic low doses of cyclophosphamide. 

Dacarbazine is a synthetic compound that functions as an alkylating agent following metabolic activation by liver microsomal enzymes by oxidative N-demethylation to the monomethyl derivative. This metabolite spontaneously decomposes to 5-aminoimidazole-4-carboxamide, which is excreted in the urine, and diazomethane. The diazomethane generates a methyl carbonium ion that is believed to be the likely cytotoxic species. Dacarbazine is administered parenterally and is not schedule-dependent. It produces marked nausea, vomiting, and myelosuppression. Its major applications are in melanoma, Hodgkin s disease, and soft tissue sarcomas. 

DACARBAZINE IL-2 J- efficacy of dacarbazine l AUC of dacarbazine due to i volume of distribution The clinical significance is uncertain as both drugs are used in the treatment of melanoma. It may be necessary to monitor clinically and by other appropriate measures of clinical response... 

Koriech OM, Shukla VS. Dacarbazine (DTIC) in malignant melanoma reduced toxicity with protection from light. Clin Radiol 1981 32 53-55. 

In a phase III trial in 190 patients with metastatic melanoma, sequential chemotherapy with dacarbazine, cisplatin, and vinblastine plus interferon alfa and aldesleukin modestly increased the response rates and produced considerably more frequent and severe adverse effects than chemotherapy alone (128). In particular, severe episodes of anemia and thrombocytopenia that required blood or platelet transfusions were 2-6 times more frequent in the chemotherapy group. 

Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Seipp CA, Einhorn JH, White DE, Steinberg SM. Prospective randomized trial of the treatment of patients with metastatic melanoma nsing chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol 1999 17(3) 968-75. 

Dacarbazine is converted to an active metabolite that is thought to be an alkylating agent. It has been used to treat metastatic melanoma and, in combination regimens, soft-tissue sarcomas and Hodgkin s disease. 

Temozolomide is structurally related to dacarbazine and is thought to act via the same active metabolite. It has been used to treat malignant gliomas and malignant melanoma. 

Treudler R, Georgieva J, Geilen CC, Orfanos CE. Dacarbazine but not temozolomide induces phototoxic dermatitis in patients with malignant melanoma. J Am Acad Dermatol 2004 50(5) 783-5. 

Phototoxic reactions occurred in 10 patients with malignant melanoma when they were given dacarbazine (6). In five patients who were tested there was increased sensitivity to ultraviolet A patch-testing in six showed no type IV allergies. In five patients oral temozolomide did not cause phototoxicity. 

A 26-year-old man with a malignant melanoma had two episodes of acute severe rhabdomyolysis after each exposure to a chemotherapy regimen containing interferon alfa and dacarbazine (310). As a few cases of... 

Hauschild A, MoUer M, Lischner S, Christophers E. Repeatable acute rhabdomyolysis with multiple organ dysfunction because of interferon alpha and dacarbazine treatment in metastatic melanoma. Br J Dermatol 2001 144(1) 215-16. 

WD is a 24-year-old woman with metastatic melanoma, who is being treated with cisplatin, dacarbazine, IL-2, and interferon-a. What precautions should be taken while she is being treated ... 

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