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Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients

2005; Elsevier BV; Volume: 64; Issue: 1 Linguagem: Inglês

10.1016/j.ijrobp.2005.06.037

1879-355X

B. Baujat, Hélène Audry, Jean Bourhis, Anthony T.�C. Chan, Haluk Onat, Daniel T. T. Chua, Dora L.�W. Kwong, Muhyi Al‐Sarraf, Kwan-Hwa Chi, Masato Hareyama, Sing Fai Leung, Kullathorn Thephamongkhol, Jean‐Pierre Pignon,

Head and Neck Surgical Oncology

Objectives: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. Methods and Materials: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log–rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. Results: Eight trials with 1753 patients were included. One trial with a 2 × 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71–0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67–0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. Conclusion: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT. Objectives: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. Methods and Materials: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log–rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. Results: Eight trials with 1753 patients were included. One trial with a 2 × 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71–0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67–0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. Conclusion: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT. In reply to Drs. Huncharek and KupelnickInternational Journal of Radiation Oncology, Biology, PhysicsVol. 65Issue 3PreviewDr. Huncharek finds it difficult to understand that his aggregated data meta-analysis (AD-MA) on the effect of chemotherapy in locally advanced nasopharyngeal carcinoma was not cited by our individual patient data meta-analysis (IPD-MA) (1). We cited only a more recent AD-MA (2) that included more trials (10 vs. 6) and used a better method. Huncharek et al. (3) calculate odds ratios based on survival rates at a particular point in time. This method may lead to biased results (4). Langendijk et al. Full-Text PDF In regards to Baujat et al.: Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients (Int J Radiat Oncol Biol Phys 2006;64:47–56)International Journal of Radiation Oncology, Biology, PhysicsVol. 65Issue 3PreviewWe read with great interest the recent article by Baujat et al., dealing with the management of locally advanced nasopharyngeal carcinoma (1), and we appreciate their confirming our prior results published in 2001. We do find it difficult to understand how our paper published in 2001 in the Journal of the American Journal of Clinical Oncology was overlooked (2). Our work has been cited by a number of other investigators, and one of us (M.H.) presented this work as an invited speaker at the Second International Chicago Symposium on Cancers of the Chest, and Head and Neck, October 4–6, 2001, Chicago, IL. Full-Text PDF