Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease.
BACKGROUND
Randomized trials have demonstrated that adding a drug to a single-agent or to a two-agent regimen increased the tumor response rate in patients with advanced non-small cell lung cancer (NSCLC), although its impact on survival remains controversial.


OBJECTIVE
To evaluate the clinical benefit of adding a drug to a single-agent or two-agent chemotherapy regimen in terms of tumor response rate, survival, and toxicity in patients with advanced NSCLC.


METHODS
There were no language restrictions. Searches of MEDLINE and EMBASE were performed using the search terms non-small cell lung carcinoma/drug therapy, adenocarcinoma, large-cell carcinoma, squamous-cell carcinoma, lung, neoplasms, clinical trial phase III, and randomized trial. Manual searches were also performed to find conference proceedings published between January 1982 and June 2006.


METHODS
Data from all randomized controlled trials performed between 1980 and 2006 (published between January 1980 and June 2006) comparing a doublet regimen with a single-agent regimen or comparing a triplet regimen with a doublet regimen in patients with advanced NSCLC.


METHODS
Two independent investigators reviewed the publications and extracted the data. Pooled odds ratios (ORs) for the objective tumor response rate, one-year survival rate, and toxicity rate were calculated using the fixed-effect model. Pooled median ratios (MRs) for median survival also were calculated using the fixed-effect model. ORs and MRs lower than unity (< 1.0) indicate a benefit of a doublet regimen compared with a single-agent regimen (or a triplet regimen compared with a doublet regimen).


RESULTS
Sixty-five trials (13601 patients) were eligible. In the trials comparing a doublet regimen with a single-agent regimen, a significant increase was observed in tumor response (OR 0.42, 95% confidence interval [CI] 0.37 to 0.47, P < 0.001) and one-year survival (OR 0.80, 95% CI 0.70 to 0.91, P < 0.001) in favor of the doublet regimen. The median survival ratio was 0.83 (95% CI 0.79 to 0.89, P < 0.001). An increase also was observed in the tumor response rate (OR 0.66, 95% CI 0.58 to 0.75, P < 0.001) in favor of the triplet regimen, but not for one-year survival (OR 1.01, 95% CI 0.85 to 1.21, P = 0.88). The median survival ratio was 1.00 (95% CI 0.94 to 1.06, P = 0.97).


CONCLUSIONS
Adding a second drug improved tumor response and survival rate. Adding a third drug had a weaker effect on tumor response and no effect on survival.
Delbaldo
Catherine
C
Michiels
Stefan
S
Rolland
Estelle
E
Syz
Nathalie
N
Soria
Jean-Charles
JC
Le Chevalier
Thierry
T
Pignon
Jean-Pierre
JP
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis