Objective: To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: Participants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University. Patients enrolled (128 in total, 112 in the final analysis) between April 1, 2017, and February 28, 2018, were randomly divided into the chronochemotherapy and conventional chemotherapy groups. In the chronochemotherapy group, docetaxel was intravenously administered between 3:30 a.m. and 4:30 a.m. on day 1, followed by intravenous administration of cisplatin between 10:00 a.m. and 10:00 p.m. from day 1to day 5. In addition, 5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m. and 10:00 a.m. (2nd day) from day 1 to day 5. In the conventional chemotherapy group, docetaxel (on day 1), cisplatin (on day 2), and 5-fluorouracil (from day 1 to day 5, 120 h in total) were administered without time-specific constraints. Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays. The gross target volume (GTV) comprised the nasopharyngeal GTV and cervical lymph node GTV. The primary endpoint was immune function, quantified by measuring dendritic cell and lymphocyte subsets, whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events. Pearson Chi-square test was applied to compare total events between the groups, Mann-Whitney U test was used to compare the DC subsets and toxicities, and Wilcoxon signed-rank test was used to compare the continuous variables between the two groups. Results: Chronochemotherapy preserved immune function, as evidenced by elevated levels of myeloid dendritic cells (P = 0.394) and higher CD4/CD8 ratio (P = 0.781). No significant difference in overall response rate, measured as the sum of complete and partial response rates, was observed between the groups (P = 0.711). A reduction in the incidence of vomiting (P = 0.002), stomatitis (P = 0.028), and mucositis (P = 0.028) was observed in the chronochemotherapy group. Leukopenia incidence rate was 83.3 % and 92.3 % in the chronochemotherapy and conventional chemotherapy groups, respectively (P = 0.232). Conclusions: In patients with locoregionally advanced NPC, the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy; however, chronochemotherapy shows fewer adverse events.
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