The Efficacy And Toxicity Of S-1 Maintenance Therapy After Curative Radiochemotherapy For N3 Stage Nasopharyngeal Carcinoma

Objective This study aims to investigate the efficacy and toxicity of S-1 maintenance therapy after curative radiochemotherapy for N3 stage nasopharyngeal carcinoma(NPC).Materials and Method This retrospective study collected 130 cases of N3 stage nasopharyngeal carcinoma(NPC)who were first diagnosed in our hospital from June 2014 to December 2016.All patients were restaged according to the UICC/AJCC eighth edition of nasopharyngeal carcinoma staging criteria.All patients completed curative induction chemotherapy +concurrent radiochemotherapy /radiotherapy± adjuvant chemotherapy.130 patients were divided into control group and maintenance treatment group according to whether given maintenance therapy or not.The dose of S-1 was determined according to the body surface area(BSA): 40 mg twice a day for BSA <1.25 m2;50 mg twice a day for 1.25 m2 ?BSA<1.5 m2;and 60 mg twice a day for BSA ?1.5 m2.S-1 was given on days 1~14,4 weeks is 1 cycle for 1~2 years.S-1 Maintenance therapy will be terminated,if disease progresses,toxic reactions are intolerable,or economic reasons and so on.We analyzed the efficacy and toxicity of S-1 maintenance therapy.Using propensity score matching(PSM)correction for confounding factors to further analyze the efficacy of maintenance therapy on the prognosis of nasopharyngeal carcinoma(NPC).Result Median follow-up time 41 months.Univariate analysis showed that the 3-year OS of the control group and the maintenance treatment group were 76.3%,95.2%,P=0.046 respectively;the 3-year PFS were 61.5%,90.5% respectively,P= 0.013;the 3-year DMFS were 70.3%,90.5%,respectively,P=0.043.Maintenance therapy was a prognostic factor affecting the survival of OS,PFS,DMFS,but not LRRFS(84.9%?100%,P = 0.091).Multivariate Cox regression analysis showed that maintenance therapy was an independent prognostic factor for PFS and DMFS(P=0.014?HR=0.17,95%CI=0.041-0.703;P=0.036?HR=0.217?95%CI=0.052-0.906).Using propensity score matching(PSM)correction for confounding factors,it suggested that maintenance therapy was a prognostic factor affecting the PFS and DMFS(0.038,0.035,respectively).A total of 366 cycles,with a median 24(3-24)cycles,of maintenance therapy were administrated to in 21 patients.Of which,12 patients received 24 cycles,and another three patients received 12 cycles and one received 18 cycles.Three patients discontinued at 5-6 cycles of maintenance therapy due to repeated grade 2 leukopenia.Two patients discontinued without reasons at the end of the third and fourth cycle of maintenance therapy.The most common hematolgic toxicity was leukopenia(52.4%)and thrombocytopenia(13.3%);Non-hematological toxicity was pigmentation(57.1%),fatigue(52.4%),anorexia(33.3%)and diarrhea(19.1%).All of the common adverse reactions were grade I ~ II,no grade III ~ IV toxicity.Conclusion Distant metastasis is the main failure mode in the treatment of nasopharyngeal carcinoma(NPC),and it is very important to improve the intensity of chemotherapy for the high risk of metastasis of N3 stage nasopharyngeal carcinoma(NPC).On the basis of systemic chemotherapy,S-1 maintenance therapy is safety and effective,with good tolerance and mild side effects.Further clinical trials are required to evaluate the efficacy of S1 maintenance therapy in N3-NPC patients.