International Journal of Radiation Oncology*Biology*Physics
Clinical investigationHead and neckChemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients
Introduction
Nasopharyngeal carcinoma (NPC) is pathologically, epidemiologically, and clinically distinct from other head-and-neck cancers (1, 2). NPC is rare in the United States (except in Alaska) and Western Europe. Also, in these areas, the frequency of squamous cell carcinoma (World Health Organization [WHO] type 1) is about 25%, markedly greater than in the endemic areas. Areas of high incidence include Southern China, Southeast Asia, the Middle East, North Africa, Alaska, and Greenland. In these areas, the Epstein-Barr virus is strongly associated with NPC. Most patients have poorly or undifferentiated (WHO type 2 or 3) carcinoma and present with locally advanced disease. Nodal involvement and bilateral nodal disease are more frequently observed with NPC than with other head-and-neck cancers. NPC is commonly treated with radiotherapy (RT) and chemotherapy (2). RT at a dose of 65–75 Gy within 6–7 weeks is standard. The overall survival (OS) rate at 5 years ranges from 32% to 52% in large series of patients with locally advanced disease treated with RT alone (2). Chemotherapy has been proposed for locally advanced NPC to improve survival (1, 2). Despite 11 randomized trials comparing RT and RT plus chemotherapy in the English literature, the magnitude of the effect of chemotherapy on survival is not well-established. OS was the main endpoint in all these trials, except for one, but only two showed a beneficial effect on survival and four on relapse-free survival. Underpowered trials could account for the inconstancy of the benefit on survival, which was the case in the previously published Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) (3). The aim of the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) was to assess the impact of adding chemotherapy to RT on OS.
Section snippets
Methods and materials
The methods of the meta-analysis are specified in a protocol published in the Cochrane library (4). The meta-analysis was based on individual patient data (5) and used a method similar to that used in the MACH-NC study (3) and the Prophylactic Cranial Irradiation Overview (6).
Trial selection
Eleven trials, including 2,722 patients, were identified in the English literature. The data from one trial (229 patients) were lost at the institution (14). We received data from 10 trials. Two trials were excluded by the Steering Committee after blind review (740 patients) because they did not meet the eligibility criterion of unpredictable treatment assignment (15, 16).
We found 88 comparative trials in the Chinese literature (7) (list available on request). Twelve were selected according to
Discussion
Despite numerous trials investigating the effect of chemotherapy on NPC, to date, no consensus has been reached about the magnitude of its benefit and the optimal protocol. An individual patient data meta-analysis was therefore justified. The exhaustiveness principle of meta-analysis was impossible to reach because of the difficulties encountered when trying to include the Chinese trials. Thus, the term “pooled analysis” could also be applied to the present study. The quality of the missing
Conclusion
The addition of chemotherapy to standard RT provides a small, but significant, survival benefit in patients with NPC.This benefit is essentially observed when chemotherapy is administered concomitantly with RT. The role of induction chemotherapy and adjuvant chemotherapy given alone or added to concomitant chemotherapy is more questionable.
Acknowledgments
We are grateful to Denise Avenell for secretariat support, Francine Courtial for trial search, Catherine Hill for her comments on the manuscript, and Lorna Saint Ange for editing.
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A complete list of the members of the MAC-NPC Collaborative Group is provided in the Appendix.
Supported by the Institut Gustave-Roussy, Aventis, Sanofi-Synthelabo, and Schering-Plough who had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The authors had full access to all the data and are fully responsible for the decision to submit the paper for publication.