Georgoulias 2005.

Methods	Randomized phase III trial, multi‐center Inclusion criteria Chemotherapy‐naive, cytologically or histologically confirmed NSCLC Stage IIIB (malignant pleural effusion) or IV disease 18 to 75 years old PS: 0 to 2 ≥ 1 measurable lesion outside radiation field Absence of second primary tumor, except basal cell carcinoma of the skin or carcinoma in situ of the cervix Adequate bone marrow, renal, and hepatic function Negative pregnancy test Life expectancy > 3 months Brain metastasis allowed if irradiated and clinically and radiologically stable Radiotherapy allowed if < 25% of total bone marrow irradiated and treatment completed ≥ 4 weeks before enrollment Exclusion criteria Severe cardiopulmonary insufficiency Severe uncontrolled angina pectoris Myocardial infarction within 6 months before enrollment Active infection Severe malnutrition (loss of > 15% of body weight)
Participants	VC arm: 204 (ITT population)/43 elderly participants DG arm: 209 (ITT population)/39 elderly participants
Interventions	VC arm: vinorelbine 30 mg/m2 over 30‐minute i.v. infusion on days 1 and 8 plus cisplatin 80 mg/m2 on day 8. rhG‐CSF 150 µg/m2/d subcutaneously, given prophylactically to all participants on days 9 through 15. Cycles repeated every 3 weeks DG arm: gemcitabine 1000 mg/m2 over 30‐minute i.v. infusion on days 1 and 8 plus docetaxel 100 mg/m2 over i.v. infusion on day 8. rhG‐CSF 150 µg/m2/d subcutaneously given prophylactically to all participants on days 9 through 15. Cycles repeated every 3 weeks All participants given ondansetron and those receiving cisplatin also administered 4 mg dexamethasone, adequate hydration, and forced diuresis. DG regimen administered on outpatient basis, whereas most VC participants admitted overnight for hydration
Outcomes	Primary outcome Overall survival (defined from date of study entry to death) Secondary endpoints ORR TTP (defined from date of study entry to first evidence of disease progression) Toxicity profile
Notes	Data on elderly subgroup achieved through direct contact with study authors Planned subgroup analysis: disease stage, PS, and histology "The study was designed to detect a 4‐month difference of overall survival with an 80% power at a significance level of .05. Three hundred sixty‐two patients (181 per arm) were required in order to achieve the statistical hypothesis"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Eligible patients were centrally registered and stratified according to age, PS and stage of the 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	Low risk	Three participants died as a result of progressive disease before chemotherapy administration, whereas 5 refused treatment and 4 did not meet entry criteria in the DG group. In addition, 5 participants refused treatment and 7 did not meet entry criteria in the VG group. All participants were included in response analysis
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting bias. Additional data provided by study authors
Other bias	High risk	Study designed for general population; elderly subgroup analysis not planned