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Dacarbazine combined targeted therapy versus dacarbazine alone in patients with malignant melanoma: a meta-analysis.

Jiang G, Li RH, Sun C, Liu YQ, Zheng JN - PLoS ONE (2014)

Bottom Line: The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China; Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, 221002, China; Center for Disease Control and Prevention of Xuzhou City, Xuzhou, 221002, China.

ABSTRACT

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.

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Forest plot of adverse events between DTIC alone and DTIC combined targeted therapy.(a) nonhematologic adverse events and (b) hematologic adverse events.
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pone-0111920-g005: Forest plot of adverse events between DTIC alone and DTIC combined targeted therapy.(a) nonhematologic adverse events and (b) hematologic adverse events.

Mentions: Nausea was reported in five trials. A fixed-effects model was used because there was no significant heterogeneity in these data sets: (I2 = 31%, P = 0.21). The result showed a significant difference between the arm for DTIC combined targeted therapy and the arm for DTIC alone (combined RR = 1.22, 95% CI: 1.10–1.37, Z = 3.64, P = 0.0003) (Fig. 5a).


Dacarbazine combined targeted therapy versus dacarbazine alone in patients with malignant melanoma: a meta-analysis.

Jiang G, Li RH, Sun C, Liu YQ, Zheng JN - PLoS ONE (2014)

Forest plot of adverse events between DTIC alone and DTIC combined targeted therapy.(a) nonhematologic adverse events and (b) hematologic adverse events.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263472&req=5

pone-0111920-g005: Forest plot of adverse events between DTIC alone and DTIC combined targeted therapy.(a) nonhematologic adverse events and (b) hematologic adverse events.
Mentions: Nausea was reported in five trials. A fixed-effects model was used because there was no significant heterogeneity in these data sets: (I2 = 31%, P = 0.21). The result showed a significant difference between the arm for DTIC combined targeted therapy and the arm for DTIC alone (combined RR = 1.22, 95% CI: 1.10–1.37, Z = 3.64, P = 0.0003) (Fig. 5a).

Bottom Line: The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China; Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, 221002, China; Center for Disease Control and Prevention of Xuzhou City, Xuzhou, 221002, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus