Herbst 2004 INTACT II.

Methods	Design: parallel‐group Randomisation: yes, method not stated Blinding: double‐blind Withdrawals: not stated
Participants	Setting: multicentre study, hospital outpatient department Number eligible: 1037 Number enrolled: 1037 Number in treatment 1 group: 345 Number in treatment 2 group: 347 Number in control group: 345 Number of withdrawals (treatment 1/treatment 2/control): 3/5/4 Number completing trial (treatment 1/treatment 2/control): 342/342/341 Age range: treatment 1 median 62 years; treatment 2 median 61 years; control median 63 years Sex: 619 M, 418 F Ethnicity: treatment 1 88.5% white, 7.5% black, 4% other; treatment 2 90.4% white, 4.1% black, 5.5% other; control 91.9% white, 5.2% black, 2.9% other NSCLC diagnosis: histologically or cytologically diagnosed NSCLC; unresectable stage III or IV disease Inclusion criteria: no prior chemotherapy; age < 18 years; WHO PS 0 to 2 Exclusion criteria: presence of mixed NSCLC or small cell lung cancer; brain metastases that were newly diagnosed or had not been treated with surgery or radiation; previously treated CNS metastases or spinal cord compression in presence of clinically stable disease; less than 2 weeks since radiotherapy; unresolved toxicity from prior radiotherapy or incomplete healing from surgery; evidence of severe systemic disease; greater than trace protein or blood on repeat urinalysis; absolute neutrophils count < 2000/µL; WBC < 4000/µL; platelets < 100,000/µL; serum bilirubin greater than 1.25 times normal upper limit; ALT or AST greater than 2.5 times normal upper limit; serum creatinine greater 1.5 times normal upper limit; pregnancy; breastfeeding; hypersensitive to mannitol, corticosteroids, H2‐antagonists, antihistamines or agents formulated with polyoxyethylated castor oil Baseline characteristics of treatment/control groups: comparable
Interventions	Regime A: IV Paclitaxel 225 mg/m3 over 3 hours on day 1 of 3 week cycle immediately followed by IV carboplatin AUC of 6 mg/mL over 15 to 30 min on day 1 Treatment 1: gefitinib 250 mg/day + 6 cycles of regime A Treatment 2: gefitinib 500 mg/day + 6 cycles of regime A Control: placebo + 6 cycles of regime A
Outcomes	Overall survival Time to progression Tumour response ‐ RECIST ASEs ‐ NCI‐CTC Haematology and biochemical parameters
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "randomized to receive..." Comment: there was insufficient information to permit a clear judgement of risk of bias
Allocation concealment (selection bias)	Unclear risk	No information provided Comment: there was insufficient information to permit a clear judgement of risk of bias
Blinding (performance bias and detection bias) All outcomes	Low risk	"double‐blind" with use of placebo tablets Comment: this was judged as a low risk of bias
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information provided Intention‐to‐treat analysis performed Comment: there was insufficient information to permit a clear judgement of risk of bias
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported Comment: this was judged as a low risk of bias
Other bias	Low risk	Financial conflicts of interest declared Comment: this was judged as a low risk of bias