Objective  To explore the safety efficacy and prognostic factors for maintenance treatment with S-1 following first-line chemotherapy (CT) for metastatic nasopharyngeal carcinoma, and to provide a new option for prolonging progression-free survival (PFS) in patients.

  Methods  Patients enrolled in The Fourth Affiliated Hospital of Guangxi Medical University, The First Affiliated Hospital of Guangxi Medical University, the Second People's Hospital of Nanning, The Affiliated Hospital of Guilin Medical College, Liuzhou Traditional Chinese Medical Hospital from January 2016 to May 2019 with metastatic nasopharyngeal carcinoma who had clinically benefited from first-line CT were randomized and stratified in a 1:1 ratio to the maintenance group (CT+S1) or observation group (CT) to evaluate the safety of and PFS benefit from the maintenance treatment. The correlations of post-treatment changes in plasma EB virus DNA (EBV-DNA) and serum amyloid A (SAA) with benefit from maintenance treatment were analyzed.

  Results  In total, 203 patients were enrolled, with the median (range) follow-up duration of 19.8 (6.1-51.3) months. Among them, 183 evaluable patients had clinically benefited from first-line chemotherapy, including 88 in CT+S1 group and 95 in CT group. Compared with that in CT group, the median PFS of patients in CT+S1 group was significantly prolonged (16.2 months vs. 8.7 months, P < 0.001). In the maintenance group, patients received a median (range) of 14 (4-58) cycles of S1 treatment; the primary adverse reactions were Grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, and nausea, and all patients tolerated the treatment well with dose modification or interruption (for < 2 weeks). EBV-DNA and SAA monitoring revealed that patients whose EBV-DNA had not decreased to 0 or whose SAA continued to decrease following first-line chemotherapy could benefit from the subsequent intervention, with these indicators continuing to decrease in 48.5% (32/66) of patients. Among patients in whom evaluable lesions remained, 51.2% (44/86) experienced further remission of lesions.

  Conclusions  Maintenance treatment with S-1 following first-line chemotherapy could improve the PFS of patients with metastatic nasopharyngeal carcinoma, and the patients could tolerate the treatment well with reasonable adjustment of the dosing schedule. Patients with continuous decreases in plasma EBV-DNA and SAA and residual lesions in imaging could derive more significant clinical benefits from the maintenance treatment.