Mok 2005.

Methods	Randomized phase II trial, conducted at a single center (Department of Clinical Oncology of the Chinese University of Hong Kong) Inclusion criteria Histologically confirmed NSCLC Stage IIIB or stage IV disease 18 to 75 years of age Measurable disease at ≥ 1 site PS: 0 to 2 No previous chemotherapy Prior radiotherapy allowed as long as treatment was not targeted to primary site of measurable disease; should be given > 3 weeks before entry into the trial Exclusion criteria Brain metastasis Hypercalcemia Life‐threatening conditions Impaired renal or hepatic function Pregnant or lactating female
Participants	GE arm: 45 participants (ITT population) ‐ median age (range): 61 (38 to 70) years/number of elderly not reported CP arm: 44 participants (ITT population) ‐ median age (range): 56 (23 to 72) years/number of elderly not reported
Interventions	GE arm: gemcitabine 1000 mg/m2 over 30‐minute i.v. infusion on days 1, 8, and 15 plus etoposide 50 mg/m2 p.o. days 1 through 14, every 4 weeks GP arm: cisplatin 75 mg/m2 over 1‐hour i.v. infusion on day 1 plus gemcitabine 1000 mg/m2 over 30‐minute i.v. infusion on days 1, 8, and 15, every 4 weeks
Outcomes	Primary outcome Toxicity (assumed 30% reduction in neutropenia in GE arm over GP arm) Secondary outcomes Response rate Time‐to‐disease progression Overall survival Quality of life
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible patients who had signed informed consent were randomly assigned to the GE or the GP arm. Randomization was stratified according to disease stage (stage IIIb vs IV) and was independently performed by a Comprehensive Cancer Trial Unit at the Chinese University of Hong Kong
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment
Blinding of outcome assessment (detection bias) OS and 1y OS rate outcome	Unclear risk	No information on blinding of assessment
Blinding of outcome assessment (detection bias) Other outcomes	High risk	No information on blinding of assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	No evidence of attrition bias
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias
Other bias	Unclear risk	No separate elderly subgroup analysis