Nasopharyngeal carcinoma--review of the molecular mechanisms of tumorigenesis

Nasopharyngeal carcinoma (NPC) is a head and neck cancer rare throughout most of the world but common in certain geographic areas, such as southern Asia. While environmental factors and genetic susceptibility play important roles in NPC pathogenesis, the Epstein-Barr virus in particular has been implicated in the molecular abnormalities leading to NPC. There is upregulation of cellular proliferation pathways such as the Akt pathway, mitogen-activated protein kinases, and the Wnt pathway. Cell adhesion is compromised due to abnormal E-cadherin and beta-catenin function. Aberrations in cell cycle are due to dysregulation of factors such as p16, cyclin D1, and cyclin E. Anti-apoptotic mechanisms are also upregulated. There are multiple abnormalities unique to NPC that are potential targets for novel treatments.     

RECURRENT NASOPHARYNGEAL CARCINOMA—TWO LONG TERM DISEASE-FREE REMISSIONS WITH NON-CISPLATINUM BASED COMBINATION CHEMOTHERAPY

Two cases of locally recurrent nasopharyngeal carcinoma following maximal radiotherapy are presented. Both patients had complete resolution of disease with outpatient combination chemotherapy using Vincristine, Adriamycin and Cyclophosphamide (VAC), and are disease free, and working full time, 3 and 4 years later, respectively. The significant relapse rate of nasopharyngeal carcinoma after initial radiotherapy is outlined, and the reported limitations of radiotherapy and chemotherapy in this situation are discussed. The survival curve for this disease appears to plateau at 2–3 years. This appears to be the first reported outpatient combination chemotherapy programme to produce long term disease-free remission in recurrent disease.     

SMART (simultaneous modulated accelerated radiotherapy) for locally advanced nasopharyngeal carcinomas

BACKGROUND: Concurrent chemoradiotherapy is commonly used for locally advanced nasopharyngeal carcinoma (NPC). We retrospectively analyzed the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) with concurrent chemotherapy. METHODS: Between January 2003 and May 2005, 24 patients with stage IIB to IVB NPC underwent SMART encompassing 3 targets: gross tumor volume (GTV), high-risk subclinical disease (CTV1), and low-risk subclinical disease (CTV2). Daily fractions of 2.4, 2.15, and 1.9 Gy were delivered to GTV, CTV1, and CTV2 to a total dose of 64.8, 58.05, and 51.3 Gy in 27 fractions over 5.5 weeks, respectively. Fifteen patients received concurrent cisplatin (DDP group), and 9 received 5-fluorouracil plus cisplatin (FP group). RESULTS: With a median follow-up of 26 months (range, 17-45 months), 3-year overall and local-, regional-, and distant-progression-free survivals were 96% and 93%, 87%, and 88%, respectively. Grade 3 acute mucositis and pharyngitis were observed in 16 (67%) and 14 (59%) patients, respectively. Severe acute mucositis (100% vs 47%) and pharyngitis (100% vs 34%) were more frequently observed in the FP group than the DDP group (p < .01). CONCLUSIONS: Despite short follow-up with a small number of patients, our preliminary results demonstrated encouraging local-regional control and survival at the cost of modest increase in treatment related toxicities. The total dose and fractionation scheme of SMART used in our study is feasible with no life-threatening or fatal complications. However, the administration of fluorouracil in addition to cisplatin during SMART was associated with increased acute and late toxicities, and it should be administered with caution.