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Updated: Jul 11, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Treatments for metastatic melanoma: synthesis of evidence from randomized trials
Philip Lui1, Richard Cashin, Márcio Machado
1Leslie Dan Faculty of Pharmacy, 144 College Street, Toronto, ON, Canada M5S 3M2. philip.lui@utoronto.ca
Background:
Advanced melanomas (non-resectable Stage-III/IV) are fatal, with few effective treatments. It remains unclear if other drugs offer improvements over the standard, dacarbazine.
Purpose:
We quantified objective response rates (Complete+Partial response) of dacarbazine versus comparators for advanced cutaneous melanoma.
Methods:
We retrieved all head-to-head randomized controlled trials involving dacarbazine and other drugs/combinations. Two reviewers searched MEDLINE (1966-Jan 2006), EMBASE (1980-2006), CINAHL (1982-2006) and Cochrane library, then compared results. Differences were resolved through consensus. Rates were combined using random effects meta-analysis. chi2 tested heterogeneity; points from Jadad's method were assessed to examine study quality.
Results:
We found 48 studies having 111 active treatment arms [24 with dacarbazine monotherapy (n=1390), 75 with dacarbazine combinations (n=4962), and 12 with non-dacarbazine treatments (n=783)] treating 7135 patients. Overall, study quality was poor. Response to dacarbazine monotherapy ranged between 5.3% and 28.0% (average 15.3%), OR=1.31, CI(95%): 1.06-1.61; N=3356. Partial responses comprised 73% of successes. Only adding interferons improved response rates (OR=1.69, CI(95%): 1.07-2.68, N=778) but survival duration was not significantly longer (P=0.32), and trials with larger sample sizes found lower success rates. All other treatments alone or in combination were ineffective P>0.05.
Conclusions:
Dacarbazine generally produces poor outcomes. Adding other therapies offers minimal clinical advantages (possibly with interferons). In general, study quality was poor and sample sizes were small. This meta-analysis highlights the unmet need for effective treatment options for advanced melanoma.
Insights
Dacarbazine offers limited benefits for advanced melanoma, with minimal improvements when combined with other therapies. Further research is needed for effective advanced melanoma treatments.
Area of Science:
- Oncology
- Medical Research
Background:
- Advanced melanomas (Stage III/IV) are often fatal with limited treatment options.
- The efficacy of treatments compared to dacarbazine for advanced melanoma is not well-established.
Purpose of the Study:
- To systematically evaluate and quantify the objective response rates of dacarbazine against alternative treatments for advanced cutaneous melanoma.
- To compare the effectiveness of dacarbazine monotherapy and combination therapies with non-dacarbazine treatments.
Main Methods:
- A comprehensive meta-analysis was conducted on head-to-head randomized controlled trials.
- Searches were performed across major databases (MEDLINE, EMBASE, CINAHL, Cochrane Library) from 1966 to 2006.
- Study quality was assessed using Jadad's scale, and response rates were combined using random-effects meta-analysis.
Main Results:
- The analysis included 48 studies with 7135 patients, evaluating dacarbazine monotherapy, dacarbazine combinations, and non-dacarbazine treatments.
- Dacarbazine monotherapy showed response rates between 5.3% and 28.0% (average 15.3%).
- Adding interferons to dacarbazine improved response rates (OR=1.69), but did not significantly increase survival duration. Other combinations were ineffective.
Conclusions:
- Dacarbazine provides generally poor outcomes for advanced melanoma patients.
- Combination therapies offer minimal clinical advantages, with a potential slight benefit from interferons.
- The study highlights the need for novel and more effective treatment strategies for advanced melanoma due to poor study quality and small sample sizes in existing trials.
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