卡瑞利珠单抗联合化疗与单纯化疗在局部晚期下咽癌诱导治疗中的效果比较  

Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma

作　　者：田姝 龚洪立 侯娜娜 李瑞辰 丁浩 吴春萍 陶磊 周梁 王胜资 Tian Shu;Gong Hongli;Hou Nana;Li Ruichen;Ding Hao;Wu Chunping;Tao Lei;Zhou Liang;Wang Shengzi(Department of Radiation Oncology,Eye&ENT Hospital of Fudan University,Shanghai 200031,China;ENT Institute and Department of Otorhinolaryngology,Eye&ENT Hospital of Fudan University,Shanghai 200031,China;Department of Medical Records,Eye&ENT Hospital of Fudan University,Shanghai 200031,China)

机构地区：[1]复旦大学附属眼耳鼻喉科医院放疗科,上海200031 [2]复旦大学附属眼耳鼻喉科医院耳鼻咽喉头颈外科,上海200031 [3]复旦大学附属眼耳鼻喉科医院病史图书室,上海200031

出　　处：《中华医学杂志》2024年第26期2401-2408,共8页National Medical Journal of China

基　　金：国家自然科学基金(81502343、81972529);上海市申康医院发展中心(SHDC2020CR6011、SHDC2024CRI053);上海市科委项目(16411950100、21Y11900100、shslczdzk00801);北京白求恩公益基金会项目(2021-YJ-088-J)

摘　　要：目的比较卡瑞利珠单抗联合改良TPF方案(多西他赛、顺铂、卡培他滨)与单纯改良TPF方案诱导治疗在局部晚期可手术切除下咽鳞状细胞癌(下咽癌)保喉策略中的疗效和安全性。方法本研究为队列研究。纳入2017年1月至2023年4月在复旦大学附属眼耳鼻喉科医院诱导治疗的初治局部晚期可手术切除下咽癌(cT3-4aN0-3bM0)患者,一组采用改良TPF方案(TPF组)诱导治疗2~3周期(回顾性资料);另一组为前瞻性Ⅱ期临床试验组,采用改良TPF方案联合卡瑞利珠单抗(TPFC组)诱导治疗3周期。原发灶完全或部分缓解患者序贯根治性放疗+/-药物治疗,TPFC组放疗结束给予卡瑞利珠单抗维持治疗,给药最长达18剂;原发灶稳定或进展患者给予根治性手术,部分拒绝手术患者给予根治性放化疗。比较两组患者客观缓解率(ORR)、总生存率、无进展生存(PFS)率、喉保留率(LPR)和不良反应发生情况。结果TPFC组和TPF组分别纳入51例和44例患者。TPFC组均为男性,年龄[M(Q_(1),Q_(3))]57(35,69)岁,TPF组男43例,女1例,年龄62(46,70)岁。TPFC组ORR高于TPF组[82.4%(42/51)比63.6%(28/44),P=0.039]。随访时间24.4(18.5,31.4)个月,TPFC组2年总生存率(84.8%比64.6%,P=0.013)及2年LPR(66.6%比48.6%,P=0.045)均高于TPF组。下咽癌诱导治疗疗效不佳者手术综合治疗2年PFS率(77.9%比18.2%,P<0.001)及2年总生存率(76.9%比45.5%,P=0.005)均高于非手术综合治疗。TPFC组恶心和(或)呕吐、反应性皮肤毛细血管增生症、甲状腺功能异常及皮疹等不良反应的发生率均高于TPF组(均P<0.05),无治疗相关死亡。结论卡瑞利珠单抗联合改良TPF方案诱导治疗相比单纯改良TPF方案具有良好的疗效和安全性,提高了局部晚期下咽癌患者的LPR。Objective To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen(docetaxel,cisplatinand capecitabine)and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma.Methods A cohort study was conducted.Patients with locally advanced resectable hypopharyngeal carcinoma(cT3-4aN0-3bM0)who were treated at the Eye&ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study.One group was treated with a modified TPF regimen(TPF group)for 2-3 cycles(retrospective data),and the other group was a prospective phaseⅡtrial with a modified TPF regimen combined with carrelizumab(TPFC group)for three cycles.The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy.The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses.The patients with stable or progressive disease were given radical surgery,and those who refused the surgery were given radical chemoradiotherapy.Objective response rate(ORR),overall survival rate,progression-free survival(PFS)rate,larynx preservation rate(LPR),and adverse reactions were compared between the two groups.Results There were 51 male patients in the TPFC group,with an median age of 57(35,69)years.Meanwhile,44 patients were in the TPF group,among which 43 were male and one was female,with an median age of 62(46,70)years.The ORR of the TPFC group was higher than that of the TPF group[82.4%(42/51)vs 63.6%(28/44),P=0.039].During a median follow-up of 24.4(18.5,31.4)months,the TPFC group showed a higher 2-year survival rate(84.8%vs 64.6%,P=0.013)and 2-year LPR(66.6%vs 48.6%,P=0.045)than those in the TPF group.In patients with poor effect of induction therapy for hypopharyngeal carcinoma,surgical combination therapy significantly prolonged the 2-year PFS rate(77.9%vs 18.2%,P<0.001)and 2-year survival rate(76.9%vs 45.5%,P=0.005)than thos

关 键 词：下咽肿瘤 诱导治疗 免疫治疗 客观缓解率 保喉治疗 

分 类 号：R739.63[医药卫生—肿瘤]