International cooperative effort 

Fleck, JF: Anticancerweb 18 (06), 2019

Nasopharyngeal carcinoma has an endemic expression, predominating in Southern China, Southeast Asia and North Africa. Global epidemiological data released by the International Agency for Research on Cancer (IARC) in 2018 point to a worldwide incidence of 130,000 cases (ASR = 1.5) associated with a 73,000-absolute mortality (ASR = 0.84). However, in endemic areas it could reach as much as 25 cases / 100,000 inhabitants (a crude rate as high as lung cancer in Western World). Geographical variations require concentration of international efforts. It is a malignant tumor that originates in the nasopharyngeal epithelial cells, predominating as an undifferentiated carcinoma (type III of the WHO classification), which accounts for 95% of the diagnosis in endemic areas. It is usually associated with EBV (91.5%) and HPV (7.7%), showing a genetic susceptibility and polymorphic expression. The strong association with EBV has been used as a screening method in high-risk populations. EBV-DNA load is prognostic and a predictive factor for metastatic disease. Staging use of PET-CT is recommended with an EBV-DNA load of more than 4000 copies/ml. Low familiarity of the Western World with this disease implies special attention in the physical exam of a patient showing cervical lymph nodes enlargement, impairment of cranial nerves and/or paraneoplastic syndromes, such as hypertrophic osteoarthropathy, dermatomyositis or fever.

In May 2019, the Sun Yat-sen University Cancer Center, Ghangzhou, China published a prospective Phase III randomized trial evaluating the benefit of induction chemotherapy (IC) prior to concurrent chemoradiotherapy (CRT) for locally advanced nasopharyngeal carcinoma (LANC). The study enrolled 480 LANC-patients at a ratio of 1: 1 into a test-arm consisting of IC (three cycles of cisplatin + gemcitabine) followed by CRT versus a control arm consisting of patients treated exclusively with CRT. After a median follow-up of 42.7 months, recurrence-free survival at 3 years was 85.3% in the test-arm and 76.5% in the control-arm (HR = 0.51 P = 0.001). An early evaluation of 3 year-overall survival showed 94.6% versus 90.3%, favoring the test-arm (HR = 0.43). There was also a benefit in the distant relapse-free survival with the use of IC (HR = 0.43). However, the local failure free-survival was similar in both arms, with very close indexes (91.8% in the test-arm and 91% in the control-arm). There was higher grade 3 and 4 toxicity in the test-arm (77.7% versus 55.7%). All patients in the test-arm completed the defined protocol of intensity-modulated radiotherapy (IMRT), but only 38.9% completed all three cycles of cisplatin programmed for IMRT-concomitant administration. The median dose of cisplatin for IMRT-concomitant administration was 200 mg in the test-arm and 300 mg in the control-arm. The median time elapsed between the beginning of the last IC cycle and the initiation of CRT was 25 days, corresponding to 17 days after the last dose of gemcitabine. In the test-arm, radiosensitizing effects of gemcitabine during the IC-phase may have been responsible for observed cisplatin dose-reduction during CRT-phase. Since 5-year median expected survival for LANC (stages III to IVB) varies from 54 to 66%, the results of this study should be interpreted as immature, especially due to contradictory results previously reported by the National Cancer Center Singapore.

ASR = Age Standardized Rate WHO = World Health Organization EBV = Epstein-Barr virus HPV = Human Papilloma Virus

References:

Y. Zhang, L. Chen, G.-Q. Hu, et al: Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma, N Engl J MedMay 31^st, 2019.  DOI 10.1056/NEJMoa1905287 

Tan T, Lim WT, Fong KW, et al. Concurrent chemo-radiation with or without induction gemcitabine, carboplatin, and paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys91:952-60, 2015