A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma

Abstract

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced mel-anoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/ m2 intravenously (IV) on day I, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/~1 was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required dis-continuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.

Systemic Therapy for Unresectable Metastatic Melanoma: Impact of Biochemotherapy on Long-Term Survival

“…Dacarbazine (DTIC) alone or in multi-drug combina-tions has been extensively evaluated for efficacy as measured by the response rates and survival (Del Prete et al, 1984;Ahmann et al, 1989;Legha et al, 1989;Anderson et al, 1995;Middleton et al, 2000;Lotze et al, 2001;Millard et al, 2004). Prospectively-randomized Phase III clinical trials have failed to confirm the superiority of multi-drug chemotherapy regimens over dacarbazine alone (Buzaid et al, 1993;Chapman et al, 1999).…”

Líquido cefalorraquiano no diagnóstico de metástase cérebro-meníngea de melanoma maligno derivado de nevo melanocítico gigante congênito: relato de caso

“…Apesar disso, Legha et al citam que pelo menos dois regimes de quimioterapia têm se mostrado razoavelmente eficazes 14 . Uma combinação de cisplastina, dacarbazina e vinblastina induziram remissão em 18 (37%) de 49 pacientes com melanoma, incluindo dois dos cinco pacientes com metastases cerebrais.…”

What is the most promising strategy for the treatment of metastasizing melanoma?

“…biopsy must be considered the mandatory modality of diagnosis and treatment of all patients affected with melanomas of 1 mm thickness or more (Table 1). This simple technique has revolutionarized our approach to managing regional nodes in patients (31,32). 3) Another important aspect to be considered more seriously is that, in selected cases, surgery is now emerging as a valid therapeutic option.…”

“…Successful cloning of human CTL recognizing autologous melanoma antigens and identification of antigen peptides presented by HLA-class I were a major breakthrough in tumor immunology (29)(30)(31). In addition, precise elucidation of the functions of dendritic cells has had great impact (32).…”