Uracil–Tegafur in Early-Stage Lung Cancer
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Kato et al. (April 22 issue),1 in their randomized study of adjuvant chemotherapy with uracil–tegafur in patients with completely resected stage I adenocarcinoma, found an overall survival benefit in favor of the uracil–tegafur group (P=0.04). However, the difference between the two groups in cancer-free survival was not significant. Therefore, the overall survival benefit in the treatment group may not reflect actual disease-related survival, which is more important in evaluating the effectiveness of chemotherapy.
Ozden Altundag, M.D.
Kadri Altundag, M.D.
Hacettepe University
Ankara 6100, Turkey
kaltunda@hacettepe.edu.tr
Mehmet Gunduz, M.D., Ph.D.
Okayama University Graduate School of Medicine and Dentistry
Okayama 700-8525, Japan
References
Kato H, Ichinose Y, Ohta M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004;350:1713-1721
To the Editor: The examination of a greater number of regional lymph nodes increases the likelihood of proper staging and affects the outcome of patients with surgically resected, stage I (pathological stage number T1N0M0 or T2N0M0) non–small-cell lung cancer.1 Surprisingly, this relevant information is lacking in the report by Kato et al. on adjuvant uracil–tegafur for stage I adenocarcinoma of the lung. In the Methods section, it is not stated whether a minimal number of retrieved lymph nodes was necessary for defining node-negative, stage I disease and whether a standardized surgical procedure for lymphadenectomy in the many participating Japanese institutions was mandatory. Finally, the number of sampled lymph nodes should have been considered an additional prognostic factor and included in the multivariate analysis.
Francesco Graziano, M.D.
Ospedale di Urbino
61029 Urbino, Italy
frada@tin.it
References
Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003;21:1029-1034.
The authors reply: In response to Dr. Altundag and colleagues: although the difference in cancer-free survival between the two groups was not statistically significant, the rate of treatment failure in the uracil–tegafur group was 3.8 percentage points lower than that in the control group. The number of patients with an extrathoracic recurrence or second cancer was 44 in the uracil–tegafur group and 60 in the control group. Accordingly, the reduction in the rate of recurrences or second primary cancers appears to be the main reason for the overall improvement in survival. The nonsignificant difference in cancer-free survival does not negate this interpretation, and the nonsignificant P value is not relevant in this context.
In response to Dr. Graziano: we agree that systemic lymph-node sampling or complete lymph-node dissection is necessary for proper staging. Since complete lymph-node resection is generally undertaken as a matter of course in Japan, it was one of the criteria for entry into this trial. Although we did not collect data on the number of dissected lymph nodes, the good survival rate in the control group is similar to that of patients with resected stage I non–small-cell lung cancer who underwent excision of more than nine nodes.1
Yukito Ichinose, M.D.
National Kyushu Cancer Center
Fukuoka 811-1395, Japan
yichinos@nk-cc.go.jp
Nobuyuki Hamajima, M.D.
Nagoya University
Nagoya 466-8550, Japan
References
Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003;21:1029-1034.
Ozden Altundag, M.D.
Kadri Altundag, M.D.
Hacettepe University
Ankara 6100, Turkey
kaltunda@hacettepe.edu.tr
Mehmet Gunduz, M.D., Ph.D.
Okayama University Graduate School of Medicine and Dentistry
Okayama 700-8525, Japan
References
Kato H, Ichinose Y, Ohta M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004;350:1713-1721
To the Editor: The examination of a greater number of regional lymph nodes increases the likelihood of proper staging and affects the outcome of patients with surgically resected, stage I (pathological stage number T1N0M0 or T2N0M0) non–small-cell lung cancer.1 Surprisingly, this relevant information is lacking in the report by Kato et al. on adjuvant uracil–tegafur for stage I adenocarcinoma of the lung. In the Methods section, it is not stated whether a minimal number of retrieved lymph nodes was necessary for defining node-negative, stage I disease and whether a standardized surgical procedure for lymphadenectomy in the many participating Japanese institutions was mandatory. Finally, the number of sampled lymph nodes should have been considered an additional prognostic factor and included in the multivariate analysis.
Francesco Graziano, M.D.
Ospedale di Urbino
61029 Urbino, Italy
frada@tin.it
References
Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003;21:1029-1034.
The authors reply: In response to Dr. Altundag and colleagues: although the difference in cancer-free survival between the two groups was not statistically significant, the rate of treatment failure in the uracil–tegafur group was 3.8 percentage points lower than that in the control group. The number of patients with an extrathoracic recurrence or second cancer was 44 in the uracil–tegafur group and 60 in the control group. Accordingly, the reduction in the rate of recurrences or second primary cancers appears to be the main reason for the overall improvement in survival. The nonsignificant difference in cancer-free survival does not negate this interpretation, and the nonsignificant P value is not relevant in this context.
In response to Dr. Graziano: we agree that systemic lymph-node sampling or complete lymph-node dissection is necessary for proper staging. Since complete lymph-node resection is generally undertaken as a matter of course in Japan, it was one of the criteria for entry into this trial. Although we did not collect data on the number of dissected lymph nodes, the good survival rate in the control group is similar to that of patients with resected stage I non–small-cell lung cancer who underwent excision of more than nine nodes.1
Yukito Ichinose, M.D.
National Kyushu Cancer Center
Fukuoka 811-1395, Japan
yichinos@nk-cc.go.jp
Nobuyuki Hamajima, M.D.
Nagoya University
Nagoya 466-8550, Japan
References
Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003;21:1029-1034.