Alberola 2003.

Methods	Randomized multi‐center phase III trial Inclusion criteria Cytologically or histologically confirmed NSCLC Stage IIIB with malignant pleural effusion not amenable to radiation therapy or stage IV No previous chemotherapy 18 to 75 years of age Bi‐dimensionally measurable disease PS 0 to 2 Adequate bone marrow, hepatic, and renal function Exclusion criteria Previous cancer, except basal cell carcinoma of the skin or carcinoma in situ of the cervix Active infection; hypercalcemia or uncontrolled systemic disease Pregnancy, breast‐feeding, or inadequate contraception precautions Symptomatic brain metastasis
Participants	CV‐VI arm: 187 (ITT population) ‐ median age (range): 60 (33 to 76) years/number of elderly participants not reported CG arm: 182 (ITT population) ‐ median age (range): 59 (33 to 75) years/number of elderly participants not reported CVG arm: 188 (ITT population) ‐ median age (range): 59 (33 to 75) years/number of elderly participants not reported
Interventions	GV‐VI arm: gemcitabine 1000 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8 for 3 cycles, followed by vinorelbine 30 mg/m2 on days 1 and 8 plus ifosfamide 3 g/m2 on day 1, for 3 cycles CG arm: cisplatin 100 mg/m2 on day 1 plus gemcitabine 1250 mg/m2 on days 1 and 8, every 21 days CGV arm: cisplatin 100 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 on days 1 and 8, every 21 days
Outcomes	Primary outcome Overall survival Secondary outcomes Time‐to‐progression Response rate Toxicity
Notes	No information on number of elderly participants 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	"The randomisation process was performed centrally by random permutated blocks within strata methods. Patients were stratified according to disease stage (IIIB v IV), baseline PS (0 to 1 v 2), and centre"
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 outcome assessment
Blinding of outcome assessment (detection bias) Other outcomes	High risk	No information on blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	"From September 1998 to July 2000, 570 patients were enrolled in the study. Thirteen patients were ineligible because of unconfirmed histology (three patients), inadequate stage (four patients), prior chemotherapy (two patients), previous diagnosis of cancer (two patients), withdrawal of consent (one patient), and concurrent acute complication before chemotherapy (one patient)"
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias
Other bias	Unclear risk	No separate elderly subgroup analysis