Chemotherapy and surgery versus surgery alone in non-small cell lung cancer.
BACKGROUND
The role of pre-operative chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC) was not clear. A systematic review and quantitative meta-analysis were therefore undertaken to evaluate the available evidence from randomised trials.


OBJECTIVE
To evaluate the effect of pre-operative chemotherapy on survival in patients with non-small cell lung cancer. If adequate data are available, to investigate whether or not pre-defined patient subgroups benefit more or less from pre-operative chemotherapy.


METHODS
MEDLINE and CANCERLIT searches for randomised controlled trials (RCTs) were supplemented by information from trial registers and by handsearching relevant meeting proceedings and by discussion with relevant trialists and organisations.


METHODS
RCTs were eligible for inclusion provided the patients had been randomised between chemotherapy followed by surgery versus surgery alone and that the method of randomisation precluded prior knowledge of the treatment to be assigned.


METHODS
A systematic review and meta-analysis based on aggregate data extracted from trial publications was carried out to assess the effectiveness of pre-operative chemotherapy in NSCLC. This involved identifying eligible RCTs and extracting aggregate data from the abstracts or reports of these RCTs. Hazard ratios were calculated from published summary statistics and then combined to give pooled estimates of treatment efficacy.


RESULTS
Twelve eligible RCTs were identified. Data were available from seven RCTs including 988 patients (75% of eligible patients). Pre-operative chemotherapy increased survival with a hazard ratio of 0.82 (95%CI 0.69-0.97) P = 0.022. This is equivalent to an absolute benefit of 6%, increasing overall survival across all stages of disease from 14% to 20% at 5 years. There was no evidence of statistical heterogeneity (P = 0.980, I(2 )= 0).


CONCLUSIONS
This analysis shows a significant increase in survival attributable to pre-operative chemotherapy. This is currently the best estimate of the effectiveness of this therapy, but is based on a small number of trials and patients. This analysis was unable to address important questions such as whether particular types of patients may benefit more or less from pre-operative chemotherapy or whether the early stopping of a number of included RCTs impacted on the results. These issues may be addressed by an ongoing individual patient data (IPD) meta-analysis.
Burdett
S S
SS
MRC Clinical Trials Unit, Meta-Analysis Group, 222 Euston Road, London, UK, NW1 2DA. sb@ctu.mrc.ac.uk
Stewart
L A
LA
Rydzewska
L
L
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic