Biochemotherapy for the treatment of metastatic malignant melanoma: A systematic review

Background: The incidence of malignant melanoma has increased in recent years. Current therapies for metastatic melanoma include chemotherapy and a variety of immunotherapeutic choices. With no established standard treatment option, the evaluation of biochemotherapy is warranted. Methods: A systematic review of the literature was conducted to locate randomized controlled trials, meta-analyses, systematic reviews, and evidence-based practice guidelines published up to April 2007. Results: Nine eligible randomized controlled trials were identified, including six comparing chemotherapy alone to biochemotherapy (chemotherapy combined with interleukin-2 and interferon). Response rates were significantly higher with biochemotherapy in only two trials, although when data were pooled, biochemotherapy was superior to chemotherapy on response (relative risk, 1.52; 95% confidence interval, 1.24-1.87; p < 0.0001) but did not delay time to progression (Hazard ratio, 0.80; 95% confidence interval, 0.63-1.01; p = 0.06). Biochemotherapy was not associated with a statistically significant survival benefit in any of the individual trials or in a pooled analysis (Hazard ratio, 0.95; 95% confidence interval, 0.78-1.17; p = 0.64). Biochemotherapy is a toxic therapy, and patients are likely to experience serious hematologic, gastrointestinal, cutaneous, and constitutional toxicities, although when conducted in the correct setting, grade 3 and 4 effects appear to be manageable, and treatmentrelated death can be minimized. Conclusion: The results of available studies are inconsistent with regard to benefit (response, time-to-progression, and survival) and show consistently high toxicity rates. Therefore, biochemotherapy is not recommended for the treatment of metastatic malignant melanoma in adults. (C) 2007 Elsevier Ltd. All rights reserved.