Georgoulias 2008.

Methods	Randomized phase III trial Inclusion criteria ≥ 18 years of age Histologically or cytologically documented, unresectable stage IIIB (with carcinomatous pleural effusion) or IV NSCLC WHO PS: 0 to 2 Life expectancy ≥ 3 months Adequate bone marrow, renal, and hepatic function Previous radiotherapy (adjuvant or for palliation) provided measurable lesions outside radiation field Brain metastasis if previously irradiated with clinical or radiological improvement Exclusion criteria Active infection History of cardiac disease Malnutrition Secondary primary tumor (except basal cell carcinoma of the skin or in situ cervical carcinoma)
Participants	DG arm: 157 participants/39 elderly/median age: 73 (range 70 to 78) years. One participant (2.4%) in the D arm had ECOG PS of 2 D arm: 155 participants/42 elderly/median age: 72 (range 70 to 78) years/6 participants (15.4%) in DG arm had ECOG PS of 2 We found imbalance between treatment arms for PS (Fisher exact test, P value = 0.04; Table 13)
Interventions	DG arm: gemcitabine 1100 mg/m2 over 30‐minute intravenous (i.v.) infusion on days 1 and 8, and docetaxel 75 mg/m2 over 1‐hour i.v. infusion on day 1, repeated every 3 weeks for 6 cycles, without rhG‐CSF D arm: docetaxel 100 mg/m2 over 1‐hour i.v. infusion on day 1, every 3 weeks for 6 cycles, without rhG‐CSF For both arms, treatment administered until disease progression, unacceptable toxicity, or consent withdrawal
Outcomes	Primary outcome Overall survival (defined as time from study enrollment to death) Secondary outcomes Response rate (according to RECIST criteria) Time‐to‐tumor progression (TTP) (defined as time from study enrollment to disease progression) Duration of response (defined as time from first documented response to disease progression) Tumor‐related symptoms and quality of life assessment (using Lung Cancer Symptom Scale (LCSS) questionnaire, assessed at baseline, after 3rd and 6th cycles) Adverse events (according to NCI‐CTC criteria)
Notes	All analyses of elderly subgroups retrieved through direct contact with study author Responses analyzed on intention‐to‐treat basis Participants given ≥ 1 cycle of chemotherapy assessed for toxicity Study was prematurely closed because of predefined OS significant difference in favor of DG arm over D arm (for general population)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were centrally randomised and stratified according to age, PS (older than 65 year vs younger) PS (2 vs 0‐1) and stage of disease (IIIB vs IV)" Elderly subgroup not planned
Allocation concealment (selection bias)	Unclear risk	No information for 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	Only 10 participants not evaluable because of treatment administration (consent withdrawn; n = 7 participants), violation of entry criteria (n = 2 participants), and misdiagnosis (n = 1 participant). No data provided for elderly subgroup
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias. Additional data provided by study authors
Other bias	High risk	Study designed for general population; elderly subgroup analysis not planned. Imbalance detected for PS between treatment arms for the elderly subgroup