Twenty four RCTs (n=7,681) were included in the review: 15 fully published and nine available as abstracts only. All trials were described as randomised, multi-centre and industry-supported. Methods of randomisation were not described in detail. None of the trials reported blinding of treatment allocation.
One phase III trial (n=308) showed a significant benefit in overall survival for single-agent docetaxel 75mg/m2 three-weekly compared with best supportive care (median survival time 7.5 months versus 4.6 months, p=0.01). No difference in survival was seen for 100mg/m2 docetaxel; the incidence of febrile neutropenia was significantly higher for 100mg/m2 docetaxel than for 75mg/m2, with grade 3/4 at 22% (including three deaths) versus 2% (no deaths) of patients.
A pooled analysis of four studies (n=540) compared weekly with three-weekly administration of docetaxel and found similar survival between the schedules (relative risk 0.99, 95% CI: 0.84 to 1.16) and no significant difference in the rates of febrile neutropenia.
Two phase III non-inferiority trials showed equivalent survival for single-agent docetaxel and pemetrexed and topotecan.
Three trials compared docetaxel-based combination therapies with single agent docetaxel; none showed a significant difference in any measure of survival. Two further trials compared other single agent therapies, irinotecan and cisplatin with combination therapy and found no significant difference in survival.
One phase III trial (n=731) showed significant benefits in overall survival (hazard ratio 0.70, 95% CI: 0.58 to 0.85, p< 0.001) and quality of life for erlotinib compared with placebo. No significant difference in survival was found between gefitinib and docetaxel (one study, n = 141) and between gefitinib and placebo (one study, n=1,692).