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Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 6276-6277 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.02.0156
Platinum-Based Versus Non–Platinum-Based Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Does Cisplatin Versus Carboplatin Make a Difference?Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
Azienda Ospedaliera-Universitaria, Parma, Italy To the Editor: In the May 1, 2005, issue of the Journal of Clinical Oncology, D'Addario et al1 reported on a meta-analysis designed to compare the efficacy and toxicity of platinum-based with non–platinum-based chemotherapy in advanced non–small-cell lung cancer (NSCLC) patients. This meta-analysis was based on abstracted data from 37 randomized phase II and III studies of varying designs, which included a total of 7,633 patients. For the entire group, the authors report that the platinum-based combinations had a significantly higher response rate and 1-year survival rate compared with the non-platinum regimens. The level of toxicity of the platinum-based therapies was significantly higher for hematologic toxicity, nephrotoxicity, and nausea and vomiting. In the subset of trials with third-generation–agent combinations (14 trials, 3,307 patients), there was no significant difference in survival between non–platinum- and platinum-based regimens. In line with the American Society of Clinical Oncology's (ASCO) 2003 Guidelines on Unresectable NSCLC,2 the authors conclude that the efficacy of third-generation non–platinum-based and platinum-based therapies is superimposable, with a less favorable toxicity profile for the latter. However, in our opinion, this conclusion is weakened by an important methodologic flaw, which has not been addressed by the authors. In fact, in this meta-analysis, D'Addario et al included both cisplatin- and carboplatin-based regimens within platinum-based chemotherapy. Overall, eight carboplatin-based regimens were included in the platinum arm, and in particular, in the subset of 14 studies with third-generation–based regimens, five regimens used carboplatin as the platinum-based chemotherapy arm. The authors treated cisplatin and carboplatin as if they were the same agent. But they probably are not. Although for some tumors, such as ovarian cancer, therapeutic equivalence has been definitively proven, and for others, such as germ cell and head and neck tumors, there is some evidence for an inferiority of carboplatin compared with cisplatin, for NSCLC the results are still contradictory.3 Recently, Hotta et al4 reported, in a meta-analysis based on the abstracted data of eight trials, that cisplatin is superior to carboplatin in terms of tumor response rates but not in terms of survival. However, in a subgroup analysis of five trials, the authors noticed that when combined with taxanes or gemcitabine cisplatin might be superior to carboplatin in terms of overall survival. Because the value of this meta-analysis is limited by the fact that it is based only on published data,5 we are currently performing an individual patient meta-analysis on the same subject. At any rate, at the present time, it is not possible to affirm the true therapeutic equivalence between cisplatin and carboplatin in the treatment of advanced NSCLC. Aside from efficacy, cisplatin and carboplatin are certainly different in terms of toxicity profiles, making of D'Addario et al's conclusions about the inferior toxicity of non–platinum-containing regimens debatable. In fact, most randomized trials comparing cisplatin versus carboplatin have shown that cisplatin is associated with more nausea/vomiting and renal toxicity, whereas carboplatin produces more myelosuppression.6 Therefore, the meta-analysis indication that platinum-based regimens are associated with increased hematologic toxicity is probably true only for carboplatin but not for cisplatin. The issue of carboplatin versus cisplatin within platinum-based chemotherapy regimens would have deserved, in our opinion, a subset analysis and an appropriate discussion. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. D'Addario G, Pintilie M, Leighl NB, et al: Platinum-based versus non-platinum-based chemotherapy in advanced non-small cell lung cancer: A meta-analysis of the published literature. J Clin Oncol 23:2926-2936, 2005
2. Pfister DG, Johnson DH, Azzoli CG, et al: American Society of Clinical Oncology Treatment of Unresectable Non–Small-Cell Lung Cancer Guidelines: Update 2003. J Clin Oncol 22:330-353, 2004
3. Go RS, Adjei AA: Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol 17:409-422, 1999
4. Hotta K, Matsuo K, Ueoka H, et al: Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non–small-cell lung cancer. J Clin Oncol 22:3852-3859, 2004
5. Piedbois P, Buyse M: Meta-analysis based on abstracted data: A step in the right direction, but only a first step. J Clin Oncol 22:3839-3841, 2004
6. Rosell R, Gatzemeier U, Betticher DC, et al: Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: A cooperative multinational trial. Ann Oncol 13:539-1549, 2002
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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