Weekly docetaxel as second line chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.
BACKGROUND
Docetaxel has to be considered as the reference control arm for second line chemotherapy for advanced NSCLC. Weekly docetaxel has been compared to standard 3-weekly schedule in a randomized fashion to determine if such schedule improves survival and quality of life. We performed a literature-based meta-analysis of all randomized clinical trials (RCTs) comparing weekly over 3-weekly docetaxel in advanced NSCLC.


METHODS
All randomized trials were considered eligible. A literature-based meta-analysis was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. A fixed- and a random-effect model according to the inverse variance and the Mantel-Haenszel method were applied. Heterogeneity test was applied as well.


RESULTS
We found six RCTs (three phase III, two phase II, 1018 patients), in which data for overall survival (OS), overall response rate (ORR) and grade 3-4 (G3-4) WHO neutropenia were available. When considering only phase III RCTs, OS did not significantly differ between the two arms (RR 1.01, 95% CI 0.76, 1.42, p=0.785) with no significant heterogeneity (p=0.42). Regarding activity, no significant differences in favour of weekly docetaxel were found, although a trend for 3-weekly schedule was observed (RR 0.81, 95% CI 0.47, 1.40, p=0.485), with no significant heterogeneity (p=0.27). No differences were found in the overall population also considering the phase II trials. Regarding G3-4 neutropenia, a significant homogenous advantage in favour of weekly docetaxel was found, with an absolute benefit of 15-19%.


CONCLUSIONS
Although considering all drawbacks related to literature-based meta-analyses, weekly docetaxel seems not to improve survival when compared to 3-weekly docetaxel. The significant benefit in grade 3-4 neutropenia seems to suggest this approach in patients with NSCLC pretreated for advanced disease. The quality of life of both schedules needs to be evaluated in an individual patient data meta-analysis.
Bria
Emilio
E
Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Roma, Italy. emiliobria@yahoo.com.it
Cuppone
Federica
F
Ciccarese
Mariangela
M
Nisticò
Cecilia
C
Facciolo
Francesco
F
Milella
Michele
M
Izzo
Fiorentino
F
Terzoli
Edmondo
E
Cognetti
Francesco
F
Giannarelli
Diana
D
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D016879:Salvage Therapy; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel