Combination of Danggui Buxue Tang and concurrent chemoradiotherapy improves treatment outcomes by strengthening B cell immunity in patients with nasopharyngeal carcinoma-a double-blind, randomized trial.

Background: Adjunctive traditional Chinese medicine (TCM) has shown potential in reducing side effects of concurrent chemoradiotherapy (CCRT) and improving outcomes of patients with nasopharyngeal carcinoma (NPC). We conducted a double-blind, randomized trial to investigate the effect of Danggui Buxue Tang (DBT) in combination with definite CCRT on patients with NPC. Methods: Patients, aged 20-70 years, with untreated stage II-IVA NPC and Eastern Cooperative Oncology Group performance status 0-2 were randomly assigned (1:1) to receive DBT or placebo (1 pack after meal, thrice a day for 12 weeks). Permuted block randomization was used, with individual emergency decoding envelopes prepared to preserve blinding. Pre- and post-treatment blood sample collection for RNA-sequencing and questionnaire survey of clinical symptoms for TCM constitution were performed. The primary end point was whether DBT could improve treatment-related adverse effects and compliance. The secondary end points included determining (I) whether the patients' clinical discomfort based on TCM constitution could be improved in the DBT group and (II) differentially expressed genes (DEGs) and possible signaling pathways between the groups. DEG analysis was performed using the DESeq2 R package. The functions of these DEGs were further analyzed using gene set enrichment analysis. Analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were performed. Post-treatment follow-up (fiberscope, physical examinations, and computed tomography/magnetic resonance imaging) was scheduled monthly for 3-6 months, at 3-month intervals for 3 years, and every 4-6 months thereafter. Results: Twenty-four patients were enrolled. Eleven patients received DBT, and 13 patients received placebo. The clinical characteristics [sex, tumor (T) stage, lymph node (N) stage, clinical stage and TCM constitutions] were generally balanced between the two groups, except for younger age observed in the DBT group (P=0.03). A large proportion of patients in the DBT group received a greater cumulative concurrent chemotherapy dose without interruption of treatment duration and experienced fewer adverse effects, especially ≥ grade 2 neutropenia (P<0.1) and ≥ grade 1 anemia (P=0.3). The qi and yin deficiency of TCM constitutions before and after CCRT were similar in the DBT group, but significantly increased in the placebo group after CCRT (both, P<0.05). The majority of the upregulated DEGs were associated with B cell receptor signaling and development. DBT may have affected the outcome through the B cell receptor signaling pathway. Conclusions: DBT in combination with CCRT for NPC can increase treatment compliance, decrease the treatment-related adverse effects, and alleviate clinical discomfort based on TCM constitution. Furthermore, DBT modulated patients' immunity through the B cell receptor signaling pathway. Therefore, DBT may be a promising, well-tolerated adjunct treatment during CCRT. However, larger, multi-center trials are needed to confirm these findings; long-term survival outcomes and broader applicability need to be evaluated in diverse patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT03578575.