Zwitter 2010.

Methods	Randomized phase II trial Eligible patients Cytological or histological confirmation of stages IIIB (wet) and IV NSCLC Chemo‐naive Measurable disease not essential Had to meet at least 1 of the following exclusion criteria for a clinical trial with the standard platinum doublet Performance status 60% to 70% (Karnovsky) or Eastern Cooperative Oncology Group 2 to 3 Hemoglobin 80 to 100 g/L Renal impairment with creatinine 1.1 to 1.5 × UNL Liver impairment with bilirubin 1.1 to 1.5 × UNL Symptomatic brain metastases after radiotherapy and/or surgery Other primary malignancy, not in complete remission during past 3 years Exclusion criteria not presented
Participants	G arm: 57 participants (ITT population)/24 elderly CG arm: 55 participants (ITT population)/18 elderly
Interventions	G arm: gemcitabine 1250 mg/m2 over 20 to 30‐minute i.v. infusion on days 1 and 8, every 3 weeks for maximum of 6 cycles CG arm: gemcitabine 800 mg/m2 over 6‐hour i.v. infusion on day 1 and cisplatin 60 mg/m2 i.v. infusion on day 2, every 3 weeks for maximum of 6 cycles
Outcomes	Overall survival Progression‐free survival No information on which outcome was defined as primary or secondary
Notes	No data related to elderly subgroup analysis obtained, despite contact with study author
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were registered for the trial by e‐mail to the data manager of the unit of clinical research. Randomization between the arms A (gemcitabine as monotherapy) and B (low‐dose gemcitabine in long infusion and cisplatin at reduced dose), 1:1, was done using a computer‐generated sequence of random numbers"
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	Open‐label study considered to have unclear impact 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	"During the interval between the patient’s registration for the trial and the actual start of chemotherapy, the general condition of nine patients (four randomised into arm A and five into arm B) deteriorated to such a degree that they received supportive treatment only. These patients are not included in the statistics of the response to treatment, toxicity, quality of life, and time to progression, but remain in the trial for survival as the primary endpoint"
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias
Other bias	Unclear risk	No data available for elderly subgroup

1yOS: one‐year survival rate; ADL: activities of daily living; AGC: absolute granulocyte count; AJCC: American Joint Committee on Cancer; ALT: amino alanine transferase; ASCO: American Society of Clinical Oncology; AST: aspartate amino transferase; AUC: area under the curve; CGA: Comprehensive Geriatric Assessment; CIRS‐G: Cumulative Illness Rating Scale for Geriatrics; CNS: central nervous system; CONSORT: Consolidated Standards of Reporting Trials; ECOG: Eastern Cooperative Oncology Group; ELCWP: European Lung Cancer Working Party; EORTC: European Organization for Research and Treatment of Cancer; G‐CSF: granulocyte‐colony stimulating factor; Gy: Gray; HRQoL: health‐related quality of life; IADL: instrumental activities of daily living; ITT: intention‐to‐treat; i.v.: intravenously; LVEF: left ventricle ejection fraction; MMSE: Mini‐Mental State Examination; MUGA: multi‐gated acquisition; NCI‐CTAE: National Cancer Institute ‐ Common Terminology Criteria for Adverse Events; NSCLC: non‐small cell lung cancer; OS: overall survival; PFS: progression‐free survival; PS: performance status; QoL: quality of life; RECIST: Response Evaluation Criteria in Solid Tumors; rhG‐CSF: recombinant human granulocyte colony‐stimulating factor; RR: response rate; TTP: time‐to‐progression; UNL: upper normal limit; WHO: World Health Organization.