Familial Nasopharyngeal Carcinoma 6

Systemic Treatment for Incurable Recurrent and or Metastatic Nasopharyngeal Carcinoma 273studies involved ex vivo expansion of EBV-specificCTLs through stimulation with EBV-transformedlymphoblastoid cell lines. Combining data from thetwo trials, infusion of CTLs resulted in two completeand three partial responses in a total of 16 patientswith measureable disease, with response duration of3–23 months. Moreover, two patients with stable diseasewere progression-free for 14 and 15 months. Theonly toxicity identified was grade 1–2 inflammatoryreaction at tumor sites in three patients. Clearly, thisapproach is worthy of additional study and these areongoing. Efficacy may be improved by cytoreducingwith chemotherapy prior to CTL infusion and mightbe best applied to patients at high risk of progressionfollowing definitive therapy. Studies to define the optimalapproach are also ongoing, selecting for dendriticcells, for example, and defining ways to enhance EBVspecificimmunity. Other immunotherapy approachesare also under study (Lin et al. 2002).21.5SummaryCytotoxic chemotherapy remains the treatment ofchoice for patients with recurrent or metastatic NPC.In the past 5–10 years taxanes and gemcitabine havedemonstrated substantial efficacy and have beenadded to the armamentarium with platinating agentsand fluoropyrimidines. At this time, platin-baseddoublets appear to be generally well tolerated and ofpalliative benefit. More aggressive multidrug regimenshave been poorly tolerated and are not recommendedoutside of a trial setting. Monotherapy with anew class of agent can be considered as second- orthird-line therapy in patients with retained performancestatus. Randomized clinical trials for patientswith incurable NPC are needed and should stratifybased on known prognostic factors, considering theheterogeneity in the population. Targeted therapy inNPC is to a great extent uncharted territory, and clinicaltrials, based on sound preclinical rationale, areclearly needed. Given the near universal associationwith EBV, viral-based adoptive immunotherapy isattractive and limited experience suggests promiseand lack of significant toxicity. This approach is thesubject of ongoing and planned investigation.However, current approaches are quite expensive andrequire a high level of technical expertise; this is prohibitiveto broad clinical application or even largescaleclinical trials. Development of an internationalconsortium at centers of excellence may help overcomethese obstacles to progress.ReferencesAiroldi M, Pedani F, Marchionatti S, et al (2002) Carboplatinplus taxol is an effective third-line regimen in recurrentundifferentiated nasopharyngeal carcinoma. 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