Chrono-chemotherapy combined with IMRT in locoregionally advanced nasopharyngeal carcinoma: A prospective randomized study.

Abstract

6113 Background: Induction chemotherapy followed by radiotherapy with concurrent cisplatin is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The TPF induction regimen combined with intensity-modulated radiation therapy (IMRT) improves tumor control but causes substantial toxicity. Circadian rhythms regulate tumor biology and drug metabolism. Docetaxel, cisplatin, and 5-fluorouracil show circadian-dependent pharmacologic properties. Chrono-chemotherapy aligns drug administration with circadian rhythms and may reduce toxicity. This study compared long-term outcomes and late adverse events between chrono-chemotherapy and conventional chemotherapy combined with IMRT in LA-NPC. Methods: This single-center, prospective, randomized clinical trial was registered at ClinicalTrials.gov (NCT03196869). Between April 2017 and May 2018, 128 patients with newly diagnosed stage III–IVa nasopharyngeal carcinoma were randomly assigned to chrono-chemotherapy or conventional chemotherapy. All patients received three cycles of TPF induction chemotherapy, followed by IMRT with two cycles of concurrent cisplatin chemotherapy. Survival outcomes were analyzed using the Kaplan–Meier method and compared by log-rank test. Late toxicities were graded using CTCAE v5.0. Quality of life was assessed with the EORTC QLQ-C30 questionnaire. Results: A total of 124 patients were included in the survival analysis. No significant differences were observed between groups in 5-year overall survival (P=0.709), progression-free survival (P=0.492), distant metastasis-free survival (P=0.467), or locoregional recurrence-free survival (P=0.697). The chrono-chemotherapy group showed lower rates of xerostomia (P=0.034) and dysphagia (P=0.019). No grade ≥4 late toxicities were observed. Global health status scores were higher in the chrono-chemotherapy group (P=0.043). Conclusions: Chrono-chemotherapy combined with IMRT achieved long-term survival outcomes comparable to conventional chemotherapy in LA-NPC. This approach reduced selected late toxicities and improved overall health status. Chrono-chemotherapy may represent a toxicity-sparing treatment option. Clinical trial information: NCT03196869 . Late toxicities and quality of life. Outcome Conventional Chemotherapy Chrono-chemotherapy P value Xerostomia, n (%) 24/36 (66.7) 16/38 (42.1) 0.034 Dysphagia, n (%) 24/36 (66.7) 15/38 (39.5) 0.019 Global health status score* 58.33 (50.00–72.92) 75.00 (50.00–83.33) 0.043 *Scores derived from the EORTC QLQ-C30 questionnaire; values are presented as median (interquartile range).