Wachters 2003.

Methods	Randomized multi‐center phase III trial Eligible patients Histologically or cytologically confirmed NSCLC Stage IIIB or IV 1 measurable or evaluable tumor lesion No previous chemotherapy and radiotherapy allowed provided ≤ 25% of bone marrow irradiated and radiation completed ≥ 4 weeks before inclusion PS: 0 to 2; life expectancy > 12 weeks Adequate bone marrow, liver, and renal function Exclusion criteria Active infection Second primary malignancy (except carcinoma in situ of uterine cervix and adequately treated basal cell carcinoma of the skin and adequately treated upper respiratory malignancy) Uncorrected hypercalcaemia LVEF < 45%, as measured by MUGA
Participants	GE arm: 121 participants (ITT population) ‐ median age (range): 60 (32 to 76) years/elderly subgroup not reported GC arm: 119 participants (ITT population) ‐ median age (range): 60 (29 to 80) years/elderly subgroup not reported
Interventions	GE arm: gemcitabine 1125 mg/m2 over 30‐minute i.v. infusion on days 1 and 8 plus epirubicin 100 mg/m2 over 5‐minute bolus i.v. infusion on day 1, every 3 weeks GC arm: gemcitabine 1125 mg/m2 over 30‐minute i.v. infusion on days 1 and 8 plus cisplatin 80 mg/m2 over 3‐hour i.v. infusion on day 2. For pre‐hydration, participants in GC arm admitted to hospital for 2 days, every 3 weeks Treatment plan consisted of 5 cycles for each treatment arm, with interruptions due to tumor progression, intolerable toxicity, or participant preference. No primary prophylaxis with G‐CSF
Outcomes	Primary outcome Progresion‐free survival Secondary outcomes Overall survival Response rate Toxicity Quality of life
Notes	No information on inclusion of elderly participants nor on specific subgroup analysis, despite multiple attempts to contact study authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Eligible patients were randomised by telephone to receive either cisplatin or epirubicin both with gemcitabine"
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment
Blinding of outcome assessment (detection bias) OS and 1y OS rate outcome	Low risk	"After treatment, tumour responses were evaluated by an independent observer"
Blinding of outcome assessment (detection bias) Other outcomes	Low risk	"After treatment, tumour responses were evaluated by an independent observer"
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Three randomised patients did not receive chemotherapy because of rapidly deteriorating performance status due to progression of disease before treatment initiation. These patients were included in all analyses"
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias
Other bias	Unclear risk	No separate elderly subgroup analysis