Kubota 2008.

Methods	Randomized phase III trial, open‐label, multi‐center Inclusion criteria Cytologically or histologically confirmed unresectable NSCLC Stage IIIB (positive pleural effusion) or IV (no brain metastasis) disease Measurable or assessable disease PS (ECOG): 0 to 1 Adequate hematological, renal, and hepatic function Exclusion criteria Grade 2 or higher peripheral neuropathy Previous chemotherapy or biological therapy
Participants	VGD arm: 196 (ITT population)/63 elderly participants CP arm: 197 (ITT population)/55 elderly participants Median age at baseline: 73 (range 70 to 81) years for both groups; 79% and 85% were male, 60% and 65% had adenocarcinoma histology, 78% and 89% had stage IV disease, and 70% and 58% had ECOG PS of 1, for non‐platinum combination and platinum combination, respectively
Interventions	VGD arm: vinorelbine 25 mg/m2 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for 3 cycles. Single‐agent docetaxel (60 mg/m2) was subsequently given i.v. on day 1, every 3 weeks for a further 3 cycles. Premedications, such as antiemetic agents or corticosteroids, were given as needed. All participants were assigned 8 mg of dexamethasone orally before docetaxel administration (experimental arm) CP arm: paclitaxel 225 mg/m2 plus carboplatin AUC6 for 3 hours on day 1, every 3 weeks for 6 cycles. Participants were assigned premedication with dexamethasone, diphenhydramine, and ranitidine or cimetidine Erythropoietin‐stimulating agents were not used. G‐CSF was permitted at any time during the study, except for prophylactic use, in both groups (control arm)
Outcomes	Primary outcome Overall survival (OS survival advantage of VGD arm over CP) Secondary outcomes Progression‐free survival Response rate Toxic effects
Notes	"We calculated that we would need 200 patients per group to detect such a difference, with a power of 0·85 using a two‐sided Log‐rank test at a significance level of 0·05"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned to the experimental regimen or the standard regimen (Figure 1). After providing written informed consent, participants were registered via fax and, if eligibility was confirmed, were allocated to one of the treatment groups by computer
Allocation concealment (selection bias)	Unclear risk	"Central randomisation to each group was applied by use of a dynamic balancing algorithm to obtain a good balance between groups in terms of the stratified factors. Randomisation was done centrally by members of the Japan Multi‐National Trial Organisation (JMTO) data centre at the Translational Research Informatics Centre, Kobe, Hyogo, Japan"
Blinding of outcome assessment (detection bias) OS and 1y OS rate outcome	Unclear risk	"Neither patients nor physicians were blinded to allocated treatment." We considered the study to have unclear impact on mortality outcomes
Blinding of outcome assessment (detection bias) Other outcomes	High risk	"Neither patients nor physicians were blinded to allocated treatment"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"Eight patients (2·0%) were ineligible for analysis: five withdrew informed consent, two had other malignancies, and one had stage IIIB disease without pleural effusion" No information provided for the elderly subgroup
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting. Additional data provided by study authors
Other bias	High risk	Study designed for the general population; elderly subgroup analysis not planned