Treatment of Resected Non–Small-Cell Lung Cancer
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《新英格兰医药杂志》
To the Editor: In the randomized trial of adjuvant chemotherapy for patients with stage IB or stage II non–small-cell lung cancer reported by Winton et al. (June 23 issue),1 a statistically significant survival advantage was found overall, but no difference was observed in the subgroup of patients with stage IB cancer. Whereas a consensus emerges from several trials about the improvement in survival in stage II disease,2,3 controversy remains about the role of platinum-based adjuvant chemotherapy in patients with stage IB non–small-cell lung cancer.1,2,4 We performed a literature-based meta-analysis to explore this issue. In a population of 2353 patients (seven phase 3 trials), a statistically insignificant but strong trend favoring chemotherapy (relative risk, 0.88; 95 percent confidence interval, 0.78 to 1.01; P=0.06) was found. Heterogeneity was not significant (P=0.31). The corresponding gain in absolute benefit was 3 percent. Our results suggest that a benefit should be investigated in an appropriately powered trial. Unfortunately, the 3 percent increase in absolute benefit would require more than 5000 patients.
Emilio Bria, M.D.
Diana Giannarelli, M.S.
Edmondo Terzoli, M.D.
Regina Elena National Cancer Institute
00144 Rome, Italy
emiliobria@yahoo.it
References
Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352:2589-2597.
Douillard J, Rosell R, Delena M, et al. ANITA: phase III adjuvant vinorelbine (N) and cisplatin (P) versus observation (OBS) in completely resected (stage I-III) non-small-cell lung cancer (NSCLC) patients (pts): final results after 70-month median follow-up. J Clin Oncol 2005;23:Suppl:624s-624s. abstract.
Depierre A, Milleron B, Moro-Sibilot D, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002;20:247-253.
Strauss GM, Herndon J, Maddaus MA, et al. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB non-small cell lung cancer (NSCLC): report of Cancer and Leukemia Group B (CALGB) Protocol 9633. J Clin Oncol 2004;22:Suppl:621s-621s. abstract.
The authors reply: To our knowledge, with the exception of Cancer and Leukemia Group B (CALGB) Protocol 9633, none of the recently published or cited studies were designed, or adequately powered, to definitively detect statistically significant differential treatment effects according to stage.1,2 The very encouraging early results of CALGB 9633, which focused on stage IB alone, await confirmation with further follow-up (Strauss G: personal communication). In the JBR.10 trial, although patients with stage IB cancer do not appear to have benefited as much as those with stage II disease, it is very important to emphasize that the interaction analysis failed to detect a statistically significant difference in treatment effect according to disease stage.
Currently, the optimal approach to analyze differential treatment effects according to stage would be a formal, patient-based meta-analysis of all data from appropriately selected studies.2,3,4
We continue to believe that the available data support adjuvant chemotherapy after resection of stage IB and stage II non–small-cell lung cancer.
Timothy L. Winton, M.D.
Walter Mackenzie Health Sciences Centre
Edmonton, AB T6G 2B7, Canada
twinton@cha.ab.ca
Keyue Ding, Ph.D.
Lesley Seymour, M.D., Ph.D.
National Cancer Institute of Canada
Kingston, ON K7L 3N6, Canada
References
The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351-360.
Pisters KMW, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol 2005;23:3270-3278.
Non-small Cell Lung Cancer Collaboration Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995;311:899-909.
Parmar MKB, Torrri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998;17:2815-2834.
Emilio Bria, M.D.
Diana Giannarelli, M.S.
Edmondo Terzoli, M.D.
Regina Elena National Cancer Institute
00144 Rome, Italy
emiliobria@yahoo.it
References
Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352:2589-2597.
Douillard J, Rosell R, Delena M, et al. ANITA: phase III adjuvant vinorelbine (N) and cisplatin (P) versus observation (OBS) in completely resected (stage I-III) non-small-cell lung cancer (NSCLC) patients (pts): final results after 70-month median follow-up. J Clin Oncol 2005;23:Suppl:624s-624s. abstract.
Depierre A, Milleron B, Moro-Sibilot D, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002;20:247-253.
Strauss GM, Herndon J, Maddaus MA, et al. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB non-small cell lung cancer (NSCLC): report of Cancer and Leukemia Group B (CALGB) Protocol 9633. J Clin Oncol 2004;22:Suppl:621s-621s. abstract.
The authors reply: To our knowledge, with the exception of Cancer and Leukemia Group B (CALGB) Protocol 9633, none of the recently published or cited studies were designed, or adequately powered, to definitively detect statistically significant differential treatment effects according to stage.1,2 The very encouraging early results of CALGB 9633, which focused on stage IB alone, await confirmation with further follow-up (Strauss G: personal communication). In the JBR.10 trial, although patients with stage IB cancer do not appear to have benefited as much as those with stage II disease, it is very important to emphasize that the interaction analysis failed to detect a statistically significant difference in treatment effect according to disease stage.
Currently, the optimal approach to analyze differential treatment effects according to stage would be a formal, patient-based meta-analysis of all data from appropriately selected studies.2,3,4
We continue to believe that the available data support adjuvant chemotherapy after resection of stage IB and stage II non–small-cell lung cancer.
Timothy L. Winton, M.D.
Walter Mackenzie Health Sciences Centre
Edmonton, AB T6G 2B7, Canada
twinton@cha.ab.ca
Keyue Ding, Ph.D.
Lesley Seymour, M.D., Ph.D.
National Cancer Institute of Canada
Kingston, ON K7L 3N6, Canada
References
The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351-360.
Pisters KMW, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol 2005;23:3270-3278.
Non-small Cell Lung Cancer Collaboration Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995;311:899-909.
Parmar MKB, Torrri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998;17:2815-2834.