Familial Nasopharyngeal Carcinoma 6

Systemic Treatment for Incurable Recurrent 21and/or Metastatic Nasopharyngeal CarcinomaYe Guo and Bonnie S. GlissonCONTENTS21.1 Introduction 26721.2 Chemotherapy 26821.2.1 Platin and Fluoropyrimidines 26821.2.2 Platin-Based Multidrug Regimens 26821.2.3 Taxane-Based Regimens 26921.2.4 Gemcitabine-Based Regimens 27021.2.5 Irinotecan 27121.2.6 Long-Term Survival 27221.3 Targeted Therapy for Recurrent/Metastatic NPC 27221.4 Immunotherapy 27221.5 Summary 273References 273Ye Guo, MDDepartment of Medical Oncology, Fudan University ShanghaiCancer Center, 270 Dong An Road, Shanghai 200032,P.R. ChinaBonnie S. Glisson, MDThoracic/Head & Neck Medical Oncology Department,Unit 432, UTMD Anderson Cancer Center, Houston,TX 77230-1402, USA21.1IntroductionNasopharyngeal carcinoma (NPC) is poorly or undifferentiatedin the vast majority of cases (70%–99%depending on geographic area). This characteristichistology combined with the abundant lymphatic networkin its anatomic site of origin is most likely themajor factors contributing to the higher rate ofregional and distant metastasis when compared withsquamous carcinoma arising in other mucosal sites ofthe head and neck (SCCHN).Approximately, 20%–30% of patients with locoregionalNPC will develop locoregional or distantrecurrences, respectively, after definitive treatmentusing conventional radiation therapy (Lin et al. 2003;Lee et al. 2003). Risk of distant metastasis specificallyis directly correlated with nodal stage and level. Theincorporation of chemoradiation and, more recently,intensity-modulated radiation therapy (IMRT) intreatment have resulted in high locoregional controlrates for locally advanced NPC, such that the majorpattern of recurrence is now distant in nature (Kamet al. 2004; Wee et al. 2005).The relatively unique chemosensitivity of NPCwas first noted in the late-1970s when chemotherapywas first studied in patients with recurrent and/ormetastatic SCCHN. Distinguished by higher rates ofresponse, longer progression-free and overall survival,compared with tumors of other primary sites,the NPC data were initially subsumed in reports withmixed patient populations. Since then, patients withmetastatic NPC have largely been segregated into separatetrials or treated outside a study setting. However,no randomized trials have been reported in this particularsetting and, thus, comparative effectiveness ofvarious regimens and approaches is only estimatedby comparing the results of single arm phase II trials.The data extant suggests that chemotherapy, while