OBJECTIVES: This study compares effectiveness of fotemustine and dacarbazine in treatment of patients with malignant melanoma with or without brain metastases using a Quality Adjusted Time Without Symptoms and Toxicity (Q-TWiST) integrating efficacy, safety and quality of life (QoL) into a composite measure of effectiveness. METHODS: Clinical trial data from a published study of fotemustine versus dacarbazine were used to partition overall survival into time spent in specific health states including toxicity, no progression and disease progression. Time spent with toxicity or disease progression was weighted by an arbitrary utility weight of 0.5. Survival analyses were conducted on the partition components. Time spent with toxicity or brain metastases was another analysis. Utilities were varied for sensitivity analyses. RESULTS: The composite measure, taking into account both efficacy and safety, demonstrated that fotemustine (N=112) was significantly more effective than dacarbazine (N=117), with an increase in quality-adjusted survival compared with dacarbazine (7.35 versus 5.64 months; P = 0.044). After taking into account time spent with toxicities, disease progression was avoided for an additional 1.54 months compared with dacarbazine (P = 0.005), a gain that is clinically significant for patients with a life expectancy of 6 to 9 months. Additionally, the mean quality-adjusted time to brain metastases was 15.39 months for the fotemustine treated patients compared to 7.04 months for the dacarbazine treated patients, for a gain of 8.35 months (P = 0.057). The quality-adjusted survival adjusting for time spent with toxicity or with brain metastases also favored treatment with fotemustine, 8.03 months versus 6.25 months (P = 0.054). Sensitivity analyses demonstrated the results to be robust. CONCLUSION: Q-TWiST analyses integrates efficacy, safety and QoL into a measure more appropriate for the assessment of cancer treatment and confirmed that fotemustine is significantly superior to dacarbazine, and provides a good alternative for the treatment of patients with malignant melanoma.