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

Abstract

BackgroundMalignant 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.MethodsWe 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.ResultsNine 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.ConclusionThese 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.

The search for a melanoma-tailored chemotherapy in the new era of personalized therapy: a phase II study of chemo-modulating temozolomide followed by fotemustine and a cooperative study of GOIM (Gruppo Oncologico Italia Meridionale)

“…Active chemotherapies in MM include alkylating agents such as dacarbazine (DTIC), temozolomide (TMZ) and fotemustine (FM). DTIC gives an overall response rate of only 10–15% with a complete response in less than 5% of patients and a survival of 7–8 months [ 9 ]. Similar overall response rates were achieved with both TMZ and FM.…”

Melanoma-targeted delivery system (part 1): Design, synthesis and evaluation of releasable disulfide drug by glutathione

“…To date, several drugs have been approved by the Food and Drug Administration for malignant metastatic melanoma, e.g. dacarbazine (DNA alkylating agent) [5], interleukin-2 [6], ipilimumab(CTLA-4 blockade) [7], vemurafenib and dabrafenib (anti-BRAF) [8]. Compared with chemotherapy, the potent specific BRAF inhibitors vemurafenib and dabrafenib have significantly improved response rates, along with progression-free and overall survival, in patients with metastatic melanoma with BR AFV600E mutations.…”

Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

“…Besides the involvement of TRPA1 in chemotherapy‐induced pain, a recent study showed its involvement in melanoma‐induced cancer pain . Because dacarbazine is the main chemotherapeutic agent used to treat metastatic melanoma, we performed a cancer pain protocol by associating the B16‐F10 melanoma tumor cell inoculation with dacarbazine administration. The association of tumor cells and dacarbazine did not produce additional nociceptive behavior because maximum nociception was achieved after a single dacarbazine administration.…”