Duration of chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials.
OBJECTIVE
To determine if it is preferable to extend chemotherapy beyond a standard number of cycles in patients receiving first-line chemotherapy for advanced non-small-cell lung cancer.


METHODS
We searched biomedical literature databases and conference proceedings for randomized controlled trials (RCTs) comparing a defined number of cycles with continuation of the same chemotherapy until disease progression, a larger defined number of cycles of identical chemotherapy, and a defined number of cycles of identical initial chemotherapy followed by additional cycles of an alternative chemotherapy. Meta-analysis was performed using the fixed effect model. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), adverse events (AE), and health-related quality of life (HRQL).


RESULTS
We found 13 RCTs including 3,027 patients. Extending chemotherapy improved PFS substantially (hazard ratio [HR], 0.75; 95% CI, 0.69 to 0.81; P < .00001) and OS modestly (HR, 0.92; 95% CI, 0.86 to 0.99; P = .03). Subgroup analysis revealed that effects on PFS were greater for trials extending chemotherapy with third-generation regimens rather than older regimens (HR, 0.70 interaction v 0.92 interaction; P = .003). Extending chemotherapy was associated with more frequent AE in all trials where it was reported and impaired HRQL in two of seven trials.


CONCLUSIONS
Extending chemotherapy, particularly with a third-generation regimen, improved PFS substantially, but OS less so. Future trials should test extending treatment with more effective and/or better-tolerated agents.
Soon
Yu Yang
YY
Sydney Cancer Center, Royal Prince Alfred Hospital, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, New South Wales, Australia.
Stockler
Martin R
MR
Askie
Lisa M
LM
Boyer
Michael J
MJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010146:Pain / Q000139:chemically induced; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome