Georgoulias 2001.

Methods	Randomized phase III trial, multi‐center Inclusion criteria Cytologically or histologically confirmed stage IIIB or IV NSCLC < 75 years old PS: 0 to 2 No previous chemotherapy Adequate bone marrow, renal, and hepatic function Previous radiotherapy in adjuvant setting or for treatment of bone metastasis provided measurable lesions were outside the radiation field Brain metastasis if previously irradiated and showing clinical and radiological improvement Exclusion criteria Active infection History of cardiac disease Malnutrition (defined as loss of > 20% of body weight)
Participants	CD arm: 205 (ITT population)/32 elderly participants ‐ median age (range): 71 (70 to 76) years; PS 1: 62.5%; stage IV: 59.4% DG arm: 201 (ITT population)/39 elderly participants ‐ median age (range): 72 (70 to 76) years; PS 1: 71.8%; stage IV: 69.2%
Interventions	CD arm: docetaxel 100 mg/m2 over 1‐hour i.v. infusion plus cisplatin 80 mg/m2 i.v. infusion on day 2 after adequate hydralazine. Antiemetic treatment of ondansetron 4 mg i.v. on day 1, and 8 mg i.v. on day 2, plus dexamethasone 4 mg i.v. before administration of cisplatin, followed by ondansetron 8 mg 3 times daily for 3 days. rhG‐CSF 150 µg/m2 from day 3 to day 9 as primary prophylaxis for neutropenia or until absolute granulocyte count ≥ 1200 µg/L on 2 consecutive measurements, after nadir DG arm: gemcitabine 1100 mg/m2 over 30‐minute i.v. infusion on days 1 and 8 plus docetaxel 100 mg/m2 over 1‐hour i.v. infusion on day 8, after administration of gemcitabine Standard antiemetic treatment of 4 mg ondansetron given intravenously before administration of chemotherapy (days 1 and 8) and 8 mg ondansetron thrice daily for 2 to 3 days. rhG‐CSF 150 µg/m2 from day 9 to day 15 for all participants as primary prophylaxis for neutropenia Participants with stable disease treated for maximum of 6 cycles; those with complete or partial response treated until disease progression or intolerable toxicity
Outcomes	Primary outcomes Response rate (according to WHO criteria) Time‐to‐progression: defined from date of study entry to first evidence of disease progression Secondary outcomes Toxicity profile (according to WHO criteria) Overall survival: defined from date of study entry to death
Notes	Data on unplanned elderly subgroup attained through direct contact with study authors Planned subgroup analysis according to stage, participant performance status, and histology "The study was designed to have 80% power to detect a 12% improvement in the overall response rate with the group 1 regimen at the one‐sided 5% level of statistical significance" "We aimed to recruit 412 patients (206 patients in each group) to achieve the statistical requirements of the fixed sample‐size design"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were centrally randomised by computer at a one‐to‐one ratio to receive either cisplatin and docetaxel (group 1) or gemcitabine and docetaxel (group 2). The allocation to either regimen was done by stratified randomisation according to age, performance status and stage of disease"
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	Open‐label study considered to have unclear influence on mortality outcomes
Blinding of outcome assessment (detection bias) Other outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	In group 1, 14 participants, and in group 2, 21not evaluable for cisplatin. 20 participants not treated, 3 of whom died from disease within 3 weeks of enrollment, with 1 refusing further treatment after first cycle, and 5 not following the protocol. No data available for evaluation of attrition bias for unplanned elderly subgroup analysis
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias. Study authors provided data for all outcomes in the unplanned elderly subgroup analysis
Other bias	High risk	Study designed for general population; elderly subgroup analysis not planned