Katakami 2006.

Methods	Randomized phase II trial Eligibility criteria Histologically or cytologically confirmed stage IIIB or IV NSCLC No prior therapy Measurable lesion by RECIST 20 to 75 years of age ECOG PS: 0 to 1 Adequate organ Life expectancy ≥ 3 months Exclusion criteria Interstitial pneumonia (pulmonary fibrosis) manifest on chest radiograph and pulmonary symptoms (non‐productive cough or dyspnea on exertion) Uncontrolled complications of heart or liver, diabetes mellitus, bleeding, peripheral neuropathy of grade 2 or worse, symptomatic brain metastases, active concomitant malignancy, pregnancy, breast‐feeding, myocardial infarction within 3 months, or other conditions rendering patient unsuitable for this study
Participants	CD arm: 68 participants (ITT population) – median age (range): 65 (31 to 75)/number of elderly not reported DG arm: 63 participants (ITT population) – median age (range): 61 (40 to 75)/number of elderly nor reported
Interventions	DG arm: docetaxel 60 mg/m2 over 1‐hour i.v. infusion on day 1 and gemcitabine 800 mg/m2 over 30‐minute i.v. infusion on days 1 and 8, every 3 weeks CD arm: cisplatin 80 mg/m2 over 1‐hour i.v. infusion and docetaxel 60 mg/m2 over 1‐hour i.v. infusion on day 1, every 3 weeks.
Outcomes	Primary outcome Response rate (designed for non‐inferiority analysis) Secondary outcomes Overall survival Progression‐free survival Response rate Adverse events
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were randomly allocated to receive DC or DG stratified by study centre, disease stage (IIIB or IV) and sex"
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 assessors for OS and 1yOS but study considered to have unclear impact on mortality outcomes
Blinding of outcome assessment (detection bias) Other outcomes	High risk	No information on blinding of outcome assessors for other outcomes
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Two patients in the DG arm did not receive any protocol treatment. One patient suffered from uncontrollable atrial fibrillation, and the investigator decided against this patient receiving protocol treatment. The other patient had a massive hematemesis from a gastric cancer that was discovered after enrolment (second primary). Because two patients were deemed ineligible, 131 patients were evaluated for survival, response, and toxicity"
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting
Other bias	Unclear risk	Study was stopped because of toxicity before target population was enrolled. "The planned patient number was 150 (75 in each arm). However, an unexpected high incidence of grade 3 interstitial lung disease (ILD) was identified exclusively in DG arm by the Adverse Event Reporting system. The principal investigator stopped the enrolment into the trial on September 30, 2003. The Safety Committee reviewed the investigator’s report and recommended that the Japan Lung Cancer Cooperative Clinical Study Group terminate the study immediately because of lung injury in the DG arm" No data provided for the elderly subgroup