Berghmans 2013.

Methods	Randomized multi‐center phase III trial Eligible patients Histological or cytological diagnosis of non‐small cell lung cancer Advanced (unresectable or functionally inoperable) stage III or stage IV disease Availability to participate in detailed follow‐up of the protocol Evaluable or measurable lesion Informed consent Exclusion criteria Prior treatment with chemotherapy Operable resectable tumor Performance status < 60 on Karnofsky Scale History of prior malignant tumor, except non‐melanoma skin cancer or in situ carcinoma of the cervix, and cured malignant tumor (> 5‐year disease‐free interval) Polynuclear cells < 2000/mm3 Platelet cells < 100,000/mm3 Serum bilirubin > 1.5 mg/100 mL Serum creatinine > 1.5 mg/100 mL and/or creatinine clearance < 60 mL/min Perception hypoacousia Peripheral neuropathy Recent myocardial infarction (< 3 months before date of diagnosis) Congestive cardiac failure requiring medical therapy or uncontrolled cardiac arrhythmia Uncontrolled infectious disease Serious medical or psychological factors that may prevent adherence to treatment schedule
Participants	GIP arm: 231 (ITT population) ‐ median age (range): 58 (29 to 78) years/number of elderly participants not reported DP arm: 233 (ITT population) ‐ median age (range): 58 (28 to 81) years/number of elderly participants not reported IG arm: 229 (ITT population) ‐ median age (range): 59 (30 to 84) years/number of elderly participants not reported
Interventions	GIP arm: gemcitabine 1000 mg/m2 on days 1 and 8 + ifosfamide 3000 mg/m2 on day 1 + cisplatin 50 mg/m2 on day 1 DP arm: docetaxel 75 mg/m2 + cisplatin 50 mg/m2 on day 1 IG arm: ifosfamide 3000 mg/m2 + gemcitabine 1000 mg/m2 on days 1 and 8
Outcomes	Primary endpoint To determine whether cisplatin‐based chemotherapy, cisplatin‐gemcitabine‐ifosfamide, or cisplatin‐docetaxel will better improve survival in comparison with the combination gemcitabine‐ifosfamide in patients with advanced NSCLC Secondary endpoints To determine the impact of each regimen on best objective response rates To compare toxicity of the 3 regimens To determine activity of salvage regimens: docetaxel after cisplatin‐gemcitabine‐ifosfamide and after gemcitabine‐ifosfamide, and gemcitabine‐ifosfamide after cisplatin‐docetaxel To determine effectiveness of erythropoietin for control of anemia due to cisplatin
Notes	No information on number of elderly participants included nor on specific subgroup analysis performed, despite multiple attempts to contact study authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Central randomisation using a minimization algorithm was performed by calling the ELCWP central office"
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment analysis
Blinding of outcome assessment (detection bias) OS and 1y OS rate outcome	Unclear risk	Study not blinded
Blinding of outcome assessment (detection bias) Other outcomes	High risk	Study not blinded. "Each patient record will be evaluated for evaluation and response in regular meetings of the Group. Patient's original record and radiological documents have to be available at this time"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"707 patients were randomised, out of whom 14 were ineligible"
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias
Other bias	Unclear risk	No separate elderly subgroup analysis