New Patterns And Their Comprehensive Treatment Of Locally Advanced Nasopharyngeal Carcinoma In Oral Mucositis

Objectives:To evaluate the efficacy and acute toxicity of induction chemotherapy followed by concomitant intensity modulated radiotherapy (IMRT) with either weekly cetuximab or weekly cisplatin for locally advanced nasopharyngeal carcinoma.Materials and Methods:Patients with stageⅢ-Ⅳa nasopharyngeal carcinoma were randomized to two treatment groups. Both groups received2courses of docetaxel-cisplatin (T:75mg/m2, P:80mg/m2) induction chemotherapy followed by IMRT. In the concomitant phase, weekly cisplatin (30mg/m2) was used in the group A while cetuximab (400mg/m2initial dose1week before the start of radiation, then250mg/m2weekly) was used in the group B. A total dose of66-70.4Gy was delivered with the IMRT technique in30-32fractions over6-6.5weeks.Results:From March2010to August2011,46patients (22in the group A,24in the group B) were enrolled into the study. The baseline demographic and clinical characteristics of the2treatment groups were well balanced. There were no significant differences in1-year progression-free survival (PFS) rate (90.9%vs90.8%, P=.767),1-year overall survival (OS) rate (100%vs100%, P=1.0),1-year local-regional relapse-free survival (LRRFS) rate (100%vs100%, P=1.0),1-year distant metastasis-free survival (DMFS) rate (95.5%vs90.8%, P=.83) and overall objective tumor response rate (ORR,100%vs100%, P=.344) between the two groups. In the concurrent phase, grade3/4non-hematologic toxicities, such as oral mucositis, were significantly more frequent in the group B than in the group A (79.1%vs45.4%, P=.012). Conversely, grade1/2hematologic toxicities were significantly more frequent in the group A than in the group B (45.5%vs4.2%, P=.000). Moreover, compliances with therapy defined as the percentage of patients who received the complete drug therapy courses were18.2%and91.6%for group A and group B, respectively (P=.000). With regard to quality of life (QOL), the mean scores of several symptom domains such as pain and difficulty swallowing were significantly higher for the group B than for the group A during the radiotherapy. However, these domains score decreased significantly and achieved no significant difference between the two groups when they were re-evaluated three months after completion of radiotherapy.Conclusion:The short-term efficacy was similar in both groups. Although better compliance with therapy and lower incidence of hematologic toxicities were observed in the cetuximab group, the increased acute toxicities--not only cutaneous reaction, but also oral mucositis, caused a more severely impaired quality of life as compared to the weekly cisplatin group. It suggests that the new treatment regimen including cetuximab for locally advanced nasopharyngeal carcinoma had better be cautiously used in the setting of clinical research. Longer follow-up is also needed to further clarify the long-term safety and efficacy of the two treatment regimens. Objectives:To investigate trends and possible relationships of microRNA-21, microRNA-744and five inflammatory cytokines concentrations with oral mucositis severity caused by combined therapy for locally advanced nasopharyngeal carcinoma.Materials and Methods:Plasma samples were obtained from the patients in the first part of the study at the time of randomization, before initiation of radiotherapy (RT), weekly during RT, and3months after completion of RT. The levels of plasma IL-1β, IL-6, IL-10, TNF-α, and TGF-β1were detected by double antibody sandwich ELISAmethod. According to the predicted results by several microRNA target prediction programs (TargetScan, Pictar, and miRDB) and reported results in the published literatures, microRNAs that could potentially regulate the gene expression of the aforementioned cytokines were selected for detection. The expression levels of microRNAs were determined by real-time fluorescent quantitative PCR technique.Results:In the concurrent phase, TNF-α concentration in the cetuximab group was significantly higher than that in the cisplatin group (P=0.011) and decreased slowly over time. In the cisplatin group, compared with the grade1/2oral mucositis subgroup, grade3/4subgroup had a higher expression of TNF-α (P=0.002). Although no significant differences in expression levels of microRNA21and microRNA-744were found between the two groups in the concurrent phase, expression level of microRNA-21was significantly lower in the grade3/4oral mucositis subgroup than in the grade1/2subgroup from the cisplatin group (P=0.002).Conclusion:The level of TNF-α was significantly higher in the cetuximab group that experienced more severe oral mucositis during the radiotherapy. This phenomenon could be a beneficial clue to explain the initiation and development mechanisms of combined therapy (radiotherapy plus cetuximab) induced oral mucositis. In our study, TNF-α and microRNA-21showed potential ability to predict the severity of oral mucositis caused by the concurrent chemotherapy. However, whether there is an interaction between these two predictors remains to be investigated.