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Medline ® Abstract for Reference 10

of 'Systemic therapy for the initial management of advanced non-small cell lung cancer without a driver mutation'

Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.
Ardizzoni A, Boni L, Tiseo M, Fossella FV, Schiller JH, Paesmans M, Radosavljevic D, Paccagnella A, Zatloukal P, Mazzanti P, Bisset D, Rosell R, CISCA (CISplatin versus CArboplatin) Meta-analysis Group
J Natl Cancer Inst. 2007;99(11):847.
BACKGROUND: Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed.
METHODS: Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided.
RESULTS: Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy.
CONCLUSIONS: Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.
Division of Medical Oncology, University Hospital, Via Gramsci 14, 43100 Parma, Italy. aardizzoni@ao.pr.it