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Cisplatin provides a higher response rate compared with carboplatin when used to treat nonsmall-cell lung cancer (NSCLC), particularly for earlier-stage disease and for patients with advanced disease but good prognosis.
Such are the results of a study published in the Journal of the National Cancer Institute, which noted that platinum-based chemotherapy leads to a small but statistically significant improvement in survival in patients with advanced NSCLC, compared to best supportive care, or when added to a number of single agents (eg, gemcitabine, taxanes, vinorelbine).
Although carboplatin has largely replaced cisplatin as the platinum drug of choice due to its association with a lower incidence of serious side-effects (eg, neurotoxicity, nephrotoxicity), it is not known whether the two drugs have similar clinical efficacy. Researchers therefore performed an individual patient data meta-analysis comparing carboplatin and cisplatin in treating advanced NSCLC.
Nine randomised trials (n=2,968) comparing carboplatin (n=1,479) with cisplatin (n=1,489) in first-line treatment of advanced (stage IIIB–IV) NSCLC were identified and included in the analysis. Primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR) and toxicity. All analyses were carried out according to the intention-to-treat principle.
The main results for an overall median follow-up of 1,021 days were:
• Cisplatin-treated patients had a median OS of 9.1 months and a one-year survival probability of 37%; the respective figures for carboplatin-treated patients were 8.4 months and 34% (HR for risk of death with carboplatin = 1.07, 95% CI = 0.99–1.15, p=NS). However, there was statistically significant heterogeneity between treatment effects on mortality among the trials.
• Subgroup analyses found carboplatin-based chemotherapy was associated with a statistically significant increase in mortality in patients with nonsquamous tumours (HR = 1.12; 95% CI = 1.01–1.23) and in those treated with third-generation chemotherapy (HR = 1.11; 95% CI = 1.01–1.21).
• ORR was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16–1.61; p<0.001).
• Cisplatin-based chemotherapy caused more nausea and vomiting (OR = 0.42, 95% CI = 0.33–0.53, p<0.001) and renal toxicity (OR = 0.37, 95% CI = 0.15–0.88, 9=0.018), whereas carboplatin-based therapy resulted in a higher incidence of thrombocytopenia (OR = 2.27, 95% CI = 1.71–3.01, p<0.001). The incidence of neurotoxicity, leucopenia, neutropenia and anaemia did not differ between the two groups.
The authors conclude: “Based on the results of the randomised trials conducted thus far, our individual patient data meta-analysis, as well as the previous literature-based meta-analyses, cisplatin should remain the reference platinum agent for treatment of NSCLC, at least in advanced-disease patients with good prognosis and in those with earlier-stage disease”.
J Natl Cancer Inst 2007;99:828-9,847-57.
