**2. Transitional epidemiology of NPC**

NPC represents 2 to 5% of all cancers in males, it is second to laryngeal cancer in most of the Mediterranean countries ant its incidence varying from 1 in Lebanon, Egypt, Greece, Turkey to 2-5/100000 in North Africa (NA), where it's characterized by a bimodal age repartition with a first peak at adolescence (Boussen et al, 2010; Ben Abdallah M, 2010). This high frequency of children and adolescents affected by NPC in Tunisia open the discussion to reach the maximum cure rate with minimal late aftereffects (Boussen et al, 2010). Endemic NPC is highly frequent in south-east Asia with an incidence > 20/100000 compared to NA (Tse et al, 2006). During the last 10 years, authors from Singapore reported a decrease of NPC incidence especially for UCNT type. This epidemiologic transition could be attributed to a socio-economic level increase as well as diet modification, such as salted fish (rich in nitrosamines) consumption decrease (Tse et al, 2006). The same trend have been observed

Update on Medical Therapies of Nasopharyngeal Carcinoma 181

cisplatin, 5-fluorouracil (5-FU), doxorubicin, epirubicin, bleomycin, mitoxantrone, methotrexate and vinca alkaloids or more recently ifosfamide or gemcitabine(Bensouda et al,2011;Boussen et al,2010;You et al,2011). CT have been used from the nineties as adjuvant then primary CT(PCT) in NPC(Bachouchi et al,1990) confirming the chemosensitivity of NPC with a high rate of radiologic/endoscopic objective responses to PCT (Bachouchi et

RT remains is the mainstay of of NPC treatment due to its radiosensibility (Boussen et al, 2010; Chan et al, 2010; Lee et al, 1992). Loco-regional RT targets primary tumor, its regional extension and both neck sides (levels Ib–V, and retropharyngeal nodes). Consensual dose is around 70 Gy with dose-fractions of 1.8 to 2Gy, indicated for sterilization of bulky tumor volume and 50–60 Gy or 46–60 Gy for areas at high risk (Lee

The results of concurrent chemoradiotherapy (CCRT) Intergroup study 0099, made gradually this combined approach as a standard in the treatment of patients with stage III and IV NPC (Al Sarraf et al, 1998; Chan et al, 2010). Within the randomized other studies, several meta-analysis and a pooled data analysis reported a significant improvement of survival in NPC patients treated by CTRT versus RT alone (Baujat et al, 2006). The NPC meta-analysis had shown the superiority of concomitant scheme vs neoadjuvant chemotherapy. It concerned 1753 patients with N1> 2cm, N2> 3cm, N3, T4, PS 0- 1, WHO 2- 3 and a mean age of 46 years. The follow-up was < 5 years for 2 trials (299 pts), 5-9 years for 6 (1454 pts) and a median follow-up of 6 years for the whole population. Delivered radiotherapy were for tumor: 65-74 Gy, for N0 : 50-66 Gy and for N+ 60-76 Gy, by using a "classical" technique and a boost for residual N associated to concomitant cisplatin-based CT in all trials. Authors reported a benefit of concomitant scheme by increasing 5-year OS from 56% to 62% and EFS from 42% to 52% significantly better than neoadjuvant chemotherapy. Recently a meta-analysis focused on South East Asian phase III trials of CT-RT from the NPC endemic area. 1608 patients were collected from seven trials (Zhang L et al, 2010) and they reported Risk ratios (RRs) of 0.63 (95% CI, 0.50 to 0.80), 0.76 (95% CI, 0.61 to 0.93) and 0.74 (95% CI, 0.62 to 0.89) for 2, 3 and 5 years OS respectively in favor of the CCRT group. Concerning the 3-years absolute number of locoregional recurrence rate (LRR), a significant overall benefit in favor of the addition of chemotherapy was found with RR of 0.67 (95% CI, 0.49 to 0.91). A significant decrease of metastatic risk was also observed in term of 3-years absolute number of distant metastasis rate (DMR) with a RR of 0.71. The RRs were larger than that detected in the previously reported meta-analysis (including both endemic and non-endemic), and authors concluded that "the relative benefit of CCRT in

endemic population might be less than that from previous meta-analyses".

The schemes used for CTRT are mainly based on "Al Sarraf" schedule with Cisplatin 100mg/m2, every 3 weeks on D1,22,43 or weekly Cisplatin at 40mg/m2(Chan Scheme),

**6.1 CT Protocols of concomitant CT-RT** 

al,1990; Ekenel et al,2011).

et al, 1992; Chan et al, 2010).

**6. Concomitant CT-RT** 

**5. Radiotherapy** 

(Sun et al,2005) from 1992 to 2002 for the incidence Rates of NPC among Chinese Americans Living in Los Angeles County and the San Francisco Metropolitan Area with a decrease of 37% for men by 37% and only 1% in women(7). Conversely, male and female NPC world age-standardized incidence reported to be 27.5/105 and 11.3/105 respectively, seems to be stable from 1970-2007 in the Chinese endemic area of Zhongshan (Wei et al, 2010). In Tunisia (Ben Abdallah M,2010), we are observing, like in Singapore, a decreasing incidence of NPC and a projection from the North Tunisia cancer registry for 2024 suggests a significant drop of NPC incidence, while breast and colon cancer will clearly increase.
