Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

Background: Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma. Methods: We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events. Results: Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR] = 1.60, 95% confidence interval [CI]: 1.27-2.01) and 1-year survival (combined RR=1.26, 95% CI: 1.14-1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR=1.23, 95% CI: 1.10-1.36), vomiting (combined RR=1.73, 95% CI: 1.41-2.12) and neutropenia (combined RR=1.75, 95% CI: 1.42-2.16) compared to the group for DTIC alone. Conclusion: These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.