时辰诱导化疗序贯同步放化疗治疗局部晚期鼻咽癌的Ⅱ期临床研究

摘要

目的：研究TPF（多西他赛+顺铂+5-氟尿嘧啶）方案时辰诱导化疗联合调强放疗治疗局部晚期鼻咽癌的毒性反应和近期疗效。方法：初治的局部晚期鼻咽癌患者，接受诱导化疗TPF方案，多西紫杉醇75 mg/m2，静滴，d1。顺铂75 mg/m2，分5 d完成静滴给药，每天10：00～22：00。5-氟尿嘧啶750 mg/m2/d d1～d5，持续静滴，每天22：00～10：00。21 d/周期，共3个周期。随后行三维适形调强放疗（IMRT），放疗同期行紫杉醇单药增敏化疗（紫杉醇135 mg/m2，静滴，21天/周期，共2个周期）。不良反应按CT-CAEv3.0评价分级，临床疗效参照2000年实体瘤治疗疗效评价标准（RECIST）进行评价，有效率为CR+PR。结果：3个周期诱导化疗后CR为23.8%，PR为68.6%。诱导化疗序贯同步放化疗后CR为64.8%，PR为31.4%。2年总生存率91.4%，2年无进展生存率87.0%，2年无远处转移生存率88.4%。诱导化疗主要不良反应为骨髓毒性，3级以上粒细胞下降为28.6%，无3级以上肾功能损害。同期放化疗期间口腔黏膜反应最多见为81.0%，其中16.2%出现3～4级反应。整组患者无治疗相关死亡。结论：TPF方案时辰诱导化疗联合紫杉醇同期调强放化疗治疗局部晚期鼻咽癌安全、近期疗效好，远期疗效及不良反应尚需扩大病例数及继续随访。%Objective:The present study aimed to investigate the short-term efficacy and adverse effects of induction chrono-che-motherapy including docetaxe1 (TXT), cisplatin (DDP), and 5 fluorouraci1 (5-FU) followed by concomitant chemoradiotherapy in lo-co-regionally advanced nasopharyngeal carcinoma (NPC). Methods:Newly diagnosed locally advanced (Ⅲ~Ⅳb) NPC patients were enrolled in this study. All patients received three cycles of TPF regimen. The TPF chemotherapy regimen was administered as follows:TXT, 75 mg/m2, i.v. infusion, d1; DDP, 75 mg/m2, bolus infusion from 10:00 to 22:00, d1-5; and 5-FU 750 mg/m2/d bolus infusion from 22:00 to 10:00, d1-5, with 21 days each cycle, followed by concomitant IMRT and chemotherapy (paclitaxel 135 mg/m2 i.v. infu-sion, with 21 days each cycle and a total of 2 courses). Acute and late toxicities were graded according to the Common Terminology Cri-teria for Adverse Events v3.0 scoring criteria. Tumor response was evaluated using 2000 Response Evaluation Criteria in Solid Tumors criteria. Results:The CR and PR rates of induction chemotherapy were 23.8%and 68.6%, respectively;whereas the CR and PR rates of the combined modality treatment were 64.8%and 31.4%, respectively. Two-year overall survival rate was 91.4%, two-year progres-sion free survival rate was 87.0%, and two-year distant metastasis-free survival rate was 88.4%. The main side effects from induction chemotherapy include an over grade 3 granulocytopenia of 28.6%. Major toxicity from concurrent chemo-radiotherapy was oral mucosi-tis (81.0%);grade 3 to 4 oral mucositis was 16%. No treatment-related deaths occurred in this study. Conclusion:Induction chrono-che-motherapy using TPF followed by concurrent chemoradiotherapy of paclitaxel is a well-tolerated treatment with short-term efficacy and severity for locally advanced NPC. Further follow-up is required to assess the late effects and long-term efficacy.