Vuoristo 2005.

Study characteristics
Methods	Phase II parallel‐group RCT. Open label study.
Participants	Untreated and previously treated (only drugs other than dacarbazine were allowed) metastatic melanoma. Randomised participants: 106.
Interventions	Four‐arm trial: Arm A: DTIC 250 mg/m² IV daily on days 1 to 5 + IFN‐α 3x10^6 mU SC daily starting on day 8 for 6 weeks and, thereafter, 6 mU 3 times weekly SC (N = 25); Arm B: Dacarbazine 200 mg/m² IV daily on days 1 to 5, vincristine 1 mg/m² (maximum, 2 mg) IV daily on days 1 and 4, bleomycin 15 mg IV on days 2 and 5, and lomustine 80 mg orally on day 1 plus IFN‐α 3x10^6 mU SC daily starting on day 8 for 6 weeks and, thereafter, 6 mU 3 times weekly SC (N = 31); Arm C: DTIC + IFN‐α 3x10^6 mU SC daily starting on day 8 for 6 weeks and, thereafter, 6 mU 3 times weekly SC (N = 25); Arm D: Dacarbazine 200 mg/m² IV daily on days 1 to 5, vincristine 1 mg/m² (maximum, 2 mg) IV daily on days 1 and 4, bleomycin 15 mg IV on days 2 and 5, and lomustine 80 mg orally on day 1 + IFN‐α 3x10^6 mU SC daily starting on day 8 for 6 weeks and, thereafter, 6 mU 3 times weekly SC (N = 25).
Outcomes	Overall survival. Progression‐free survival. Tumour response. Toxicity.
Notes	Quality of life: not reported. Cross‐over: not allowed. Participants with brain metastasis: excluded. Median follow‐up: > 17 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The randomization was performed at the Finnish Cancer Registry and stratified for treatment arm by institution." Comment: There was insufficient information about the sequence generation process to permit judgment.
Allocation concealment (selection bias)	Unclear risk	There was insufficient information to permit judgment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	As an open label study, no blinding of participants or personnel was possible. However, we believe that in this setting (metastatic melanoma), with the treatments tested and outcomes assessed, the knowledge of which intervention was received or administered (rather than the intervention itself), could not affect the outcomes under investigation. Therefore, we judged the risk of performance bias as low.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	There was insufficient information to permit judgment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data were balanced across intervention groups, with similar reasons for missing data across groups.
Selective reporting (reporting bias)	Low risk	No differences between protocol and published report.
Other bias	Low risk	The study appeared to be free of other sources of bias.