Maruyama 2008 V‐15‐32.
Methods | Design: parallel‐group Randomisation: yes, method stated Blinding: open‐label Withdrawals: stated |
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Participants | Setting: multicentre study, hospital outpatient department Number eligible: 511 Number enrolled: 489 Number in treatment group: 245 Number in control group: 244 Number of withdrawals (treatment/control): 233/241 Number completing trial (treatment/control): 12/3 Age range: < 64 years = 275, > 65 years = 216 Sex: M 302, F 187 Ethnicity: Japanese NSCLC diagnosis: histologically or cytologically confirmed NSCLC (stage IIIB/IV) Inclusion criteria: age 20 years or older, pretreated locally advanced/metastatic (stage IIIB/IV) NSCLC, or recurrent NSCLC, NSCLC not amenable to curative surgery or radiotherapy or postoperative recurrent NSCLC, failure of prior treatment with 1 or 2 chemotherapy regimens (> 1 platinum based regimen), life expectancy of 3 months or greater, WHO PS score 0 to 2, measurable disease by RECIST, WBC count of 4.0 to 12.0 x 109 cells/L, neutrophil count < 2.0 x 109 cells/L, platelet count > 100 x 109 cells/L, serum bilirubin < 1.5 x 109 cells/L, ALT or AST < 2.5 x upper limit of reference range, serum creatinine < 1.5 mg/dL, arterial oxygen tension > 70 torr. Exclusion criteria: received last chemotherapy within 4 weeks before enrolment, received prior treatment with a docetaxel‐containing regimen or any anti‐EGFR therapy, an allergy or suspected allergy to gefitinib or docetaxel, other coexisting malignancies diagnosed within the last 5 years, with exceptions, any unresolved chronic toxicity greater than NCI‐CTC grade 2 from previous anticancer therapy, any evidence of severe or uncontrolled systemic disease, as judged by investigator, current status of pregnancy or breastfeeding, treatment with a non‐approved or investigational drug within 30 drugs before enrolment, intracerebral metastases, significant malabsorption syndrome, past history of or concurrent interstitial lung disease, idiopathic pulmonary fibrosis or pneumoconiosis, or radiation pneumonia or drug‐induced pneumonia, that required corticosteroids, fever with suspected infection or treatment with systemic corticosteroids for > 4 weeks Baseline characteristics of treatment/control groups: comparable |
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Interventions | Gefitinib 250 mg/day Docetaxel every 3 weeks as a 1‐hour intravenous infusion of 60 mg/m2 |
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Outcomes | Overall survival Progression‐free survival (PFS) Tumour response ‐ RECIST ASEs ‐ NCI‐CTC |
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Notes | — | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Quote: "randomly assigned by using stratification..." Comment: this was judged as a low 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 | No blinding but review authors judge that outcome is not likely to be influenced by lack of blinding Comment: this was judged as a low risk of bias |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions presented in Figure 1. Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups. 483/489 patients analysed for safety, 387/489 (79%) analysed for response (balanced between treatment arms) Intention‐to‐treat analysis performed Comment: this was judged as a low 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 | Co‐authors have received honoraria from industry Comment: this was judged as a low risk of bias |