Annals of Oncology 17 (Supplement 10): x304–x307, 2006 doi:10.1093/annonc/mdl278 Nasopharyngeal carcinoma and therapeutic management: the place of chemotherapy J. Guigay 1 , S. Temam 2 , J. Bourhis 3 , J.-P. Pignon 4 & J.-P. Armand 1 1 Department of Medical Oncology, 2 Department of Head and Neck Surgery, 3 Department of Radiotherapy and 4 Department of Biostatistics and Epidemiology, Institut de Cance ´rologie Gustave Roussy, Villejuif, France introduction Nasopharyngeal carcinoma (NPC) differs from others head and neck cancers by many points. Its incidence remains high in some parts of the globe, in southern China, Southeast Asia and North Africa. In North Africa there are two peaks of age-specific incidence, in young (between 10 and 20 years old) and adult patients (50 years old) [1, 2]. Among the three histological types, the Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) (WHO type 2 and 3) is the most frequent in endemic areas; however, squamous cell carcinoma (WHO type 1) is more common in Europe and has a worse prognosis [2]. The role of Epstein–Barr virus (EBV) infection in the NPC carcinogenesis is well documented but non-exclusive and environmental factors and genetically determined susceptibility may play a role [1]. prognostic factors Tumor develops initially in the walls of the nasopharynx, without any symptoms, explaining a usual late diagnosis. Later, locoregional invasion may extend to the cranial nerves and the base of the skull, which increases the risk of local failure after radiotherapy [3]. Lymph node involvement is frequent. Node-positive patients (N+) have a high risk of distant metastasis (bone, lung and liver metastasis) and a decreased survival: patients with N1 and N2/N3 disease have a 33% and 70% incidence of distant metastasis at 10 years respectively [4]. TNM stage is, accordingly, the major prognostic factor, but is controversial as two classifications are currently used: Ho’s and UICC2003 classification [2]. Among biological parameters, which could be useful prognostic markers, pretreatment and post-radiotherapy EBV DNA levels have been correlated with outcome and survival [5, 6]. treatment: new approaches Usually unresectable, NPC is more responsive to radiotherapy and chemotherapy than other head and neck cancers. Radiotherapy alone has been the first curative treatment of NPC and remains the standard treatment of the initial stages I, without node involvement, yielding a 10-year survival rate of 98% [4]. If the place of chemotherapy is not discussed in metastatic disease, its role and modality in the initial management remains controversial. In terms of efficacy, recent trials and meta-analysis highlight the need to adjunct chemotherapy to radiotherapy: concomitant radiochemotherapy appears now to be superior to radiotherapy alone and can be defined as the standard treatment in 2006 for locally advanced (T2B and more) and/or N+ patients. In this review we focus on these recent advances. concurrent chemo-radiotherapy: a standard treatment for locoregionally advanced NPC Until now, results of six randomized trials and two meta-analyses [7–9] had shown that concomitant chemotherapy and radiotherapy are superior to radiotherapy alone in terms of relapse-free and overall survival, but the real benefit was not clear. The results of the last meta-analysis on behalf of the MAC-NPC collaborative group have recently been published [10]. This study used updated individual patient data from eight randomized trials comparing chemotherapy plus radiotherapy versus radiotherapy alone in locally advanced NPC. The trials included 1753 patients, and 728 deaths (42%) occurred. All trials used conventional radiotherapy and cisplatin-based chemotherapy. A small, but significant benefit was found for overall survival (6% at 5 years) and event-free survival (10% at 5 years) with the addition of chemotherapy (Figure 1). The benefit on survival was essentially observed when chemotherapy was administered concomitantly with radiotherapy (Figure 2). The only excess treatment-related deaths were observed in the induction chemotherapy trials. However, chemotherapy lowered the risk of locoregional and distant failure whatever the timing of chemotherapy. This meta-analysis confirms the role of concurrent chemo-radiotherapy as a standard treatment for locoregionally advanced NPC. However, the higher incidences of acute and late toxicities need the development of conformal radiotherapy techniques and new cytotoxic agents [9, 11, 12]. ª 2006 European Society for Medical Oncology by guest on August 19, 2015 http://annonc.oxfordjournals.org/ Downloaded from