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. Phase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. Several different combination biochemotherapy regimens have been studied in phase II studies and in that pahse III study. 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. Tumor response was assessed after cycles 2 and 4, then every 3 months.
Four hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001). 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."
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.