Familial Nasopharyngeal Carcinoma 6

268 Y. Guo and B. S. Glissonpalliative in effect for the vast majority of patients,can result in long-term disease control in a smallpercentage of patients, with or without the incorporationof radiation to involved sites. Beyond conventionalchemotherapy, molecularly targeted therapyand Epstein–Barr virus (EBV)-based immunotherapyapproaches hold promise. However, published experienceis minimal currently. Herein, we will review thecurrently available options for systemic treatment ofincurable recurrent and/or metastatic NPC and identifypotential avenues for future research.21.2ChemotherapyOn the basis of extrapolation from studies with neoadjuvantand concurrent regimens for NPC as well asdata from studies in SCCHN of other primary sites,platin-based therapy has been most commonly investigatedand utilized in practice for patients withincurable recurrent or metastatic NPC. While therehave been no direct comparisons of various regimens,overall experience suggests that the singleagent response rates of cisplatin (28%) and carboplatin(22%) (Chan et al. 2002) are augmented by a secondactive drug, but that no major incrementalincrease in response is obtained by adding a third orfourth drug. In addition, these latter regimens havebeen quite toxic and are not commonly utilized. Themost commonly used regimens include a platin with5-fluorouracil (5-FU) or a taxane.21.2.1Platin and FluoropyrimidinesThe preclinical and clinical evidence base for the efficacyof cisplatin and 5-FU (PF regimen) in the treatmentof SCCHN and curative-intent treatment oflocoregional NCP is substantial. Perhaps because it iscommonly used during definitive therapy, its study inthe setting of recurrent/metastatic NPC is not exhaustive.In a small phase II study conducted in Singapore(Au and Ang 1994), 24 chemotherapy-naïve patientswere treated with cisplatin at 100 mg/m 2 , and 5-FU1,000 mg/m 2 daily by continuous infusion days 1–5,every 3 weeks. Responses were observed in 16/24 (66%);three patients responded completely. Median progression-freeand overall survival times were 8 and 11months, respectively. There was no treatment-relatedmortality, and the most common grade 3–4 toxicity wasgranulocytopenia, occurring in 10/24 (41%) patients.With the goal of reducing toxicity related to cisplatin,carboplatin was combined with 5-FU and studied in alarger trial of 42 patients (Yeo et al. 1996). Although theoverall response rate was lower at 38%, the completeresponse rate of 17% and median survival of 12 monthswas similar to that obtained in the smaller trial withcisplatin. Notably, in a randomized trial of patients withnewly diagnosed NPC, equivalent efficacy and reducedtoxicity was observed with concurrent carboplatin andadjuvant carboplatin/5-FU, compared with cisplatin(Chitapanarux et al. 2007). Certainly, in a palliativeintentsetting, it seems reasonable to consider use ofcarboplatin, especially in patients who have had substantialcisplatin exposure during curative-intent therapyand who may have persistent renal or neurologictoxicity, uncontrolled nausea/vomiting, or hearing loss.The oral fluoropyrimidine, capecitabine was givenas monotherapy in a phase II trial of 49 patients withrecurrent/metastatic NPC with partial and completeresponse rates of 31% and 6%, respectively (Chuaet al. 2008). Median progression-free and overall survivalrates were 5 and 14 months, respectively. Hand–foot syndrome (HFS), seen in 86% of patients, wassevere grade in 25%. This toxicity was especially severeat a dose of 1.25 g/m 2 bid for 14 days in the first 37patients. A dose reduction to 1 g/m 2 given in the sameschedule reduced the incidence and severity of HFS inthe final 12 patients. Capecitabine and cisplatin werecombined in a prospective trial of 48 patients withsimilar efficacy outcomes as PF in a recent phase IItrial of patients with metastatic disease (Li et al. 2008).Li et al. reported an overall response rate of 62%(30/48) and median progression-free and overall survivalrates of 7.7 and 13.3 months, respectively. Toxicityprofile was similar to PF and judged manageable withneutropenia (15%), the only grade 3–4 effect observedin greater than 10% of patients. Severe grade HFS wasseen in 4% of patients with capecitabine dose 1 gm/m 2bid for 14 days. The convenience of oral administrationand the avoidance of prolonged intravenous infusionmake this an attractive option for patients whohave a reasonable progression-free interval followingprior fluoropyrimidine therapy.21.2.2Platin-Based Multidrug RegimensBecause NPC is chemosensitive, multiple activeagents have been identified and studied further inplatin-based regimens.