Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials.
Evidence suggests that platinum-based regimens confer a better survival in patients with non-small cell lung carcinoma (NSCLC). However, evidence is lacking regarding the specific effects of cisplatin or carboplatin when compared to non-platinum-based doublets.


METHODS
Meta-analysis of all randomized trials comparing non-platinum-based with platinum-based doublet regimens given as first-line treatment for NSCLC. Relative risks were calculated for all outcomes ascertained. Sensitivity analysis, using methodological quality of the trials and different measures of effect, was undertaken.


RESULTS
Seventeen trials, comprising 4920 patients were included. The use of platinum-based doublet regimens was associated with a slightly higher survival at 1 year (RR=1.08, 95% CI 1.01-1.16, p=0.03), better partial response (RR=1.11, 95% CI 1.02-1.21, p=0.02), with a higher risk of anemia, nausea, and neurotoxicity. Cisplatin-based doublet regimens improved survival at 1 year (RR=1.16, 95% CI 1.06-1.27, p=0.001), complete response (RR=2.29, 95% CI 1.08-4.88, p=0.03), partial response (RR=1.19, 95% CI 1.07-1.32, p=0.002) with an increased risk of anemia, neutropenia, neurotoxicity and nausea. Conversely, carboplatin-based doublet regimens did not increase survival rate at 1 year (RR=0.95, 95% CI 0.85-1.07, p=0.43). There was a statistically significant difference between the effect of cisplatin compared to carboplatin (p=0.05). Carboplatin-based doublet regimen included a higher risk of anemia and thrombocytopenia, but no increased nausea and/or vomiting, contrarily to cisplatin. Sensitivity analyses showed that the results were robust to the exclusion of lesser quality trials and the choice of the measure of effect.


CONCLUSIONS
We provide additional evidence that cisplatin, but not carboplatin-based doublet regimens are associated with a slightly better survival compared to non-platinum-based doublet regimens. Side effects of cisplatin- and carboplatin-based regimens differ between each other and when compared to non-platinum doublets. Although this analysis has limitations, it may provide valuable information to clinicians when choosing the appropriate regimen for patients with non-small cell lung cancer.
Rajeswaran
Anand
A
Faculty of Biology and Medicine, University of Lausanne, Switzerland.
Trojan
Andreas
A
Burnand
Bernard
B
Giannelli
Massimo
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic
D016190:Carboplatin; D002945:Cisplatin