h-R3联合放疗治疗局部晚期鼻咽癌的Ⅱ期临床研究

Phase Ⅱ Clinical Trial of h-R3 Combined Radiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma

背景与目的:目前临床应用的抗表皮生长因子受体(epidermal growth factor receptor,EGFR)的单克隆抗体易产生人抗鼠抗体反应,影响治疗效果。本研究评估人源化的抗EGFR单克隆抗体h-R3联合放疗对局部晚期鼻咽癌的近、远期疗效及毒性反应。方法:将免疫组化证实有EGFR中、强度表达的Ⅲ～Ⅳb期(UICC1997)鼻咽癌初诊患者随机分为单纯放疗组(单放组)和放疗联合h-R3组(联合组),两组的放疗剂量和技术基本相同,联合组在放疗期间每周一次静脉滴注h-R3100mg。用WHO标准评价两组的近期疗效,用Kaplan-Meier法估计两组的生存率。结果:本研究共纳入35例,单放组和联合组分别为17例和18例,其中联合组有1例于治疗中途退组。联合组于治疗结束时、治疗后5周及治疗后17周时的总CR率分别为72.2%、83.3%和83.3%,而单放组分别为35.3%、41.2%和47.1%(P<0.05)。中位随访时间31.9个月(4.2～40.7个月),单放组的3年局部区域控制率、无远处转移生存率分别为和总生存率93.8%、100%和88.2%,联合组分别为100%、88.2%和94.4%,两组间的差异无统计学意义(P>0.05)。联合组除1例出现Ⅱ级呕吐外,均无任何药物不良反应发生,两组的急性放射反应差异也无统计学意义(P>0.05)。结论:h-R3是一种安全性良好的药物,有助于增强局部晚期鼻咽癌的放射灭瘤效应,但对远期疗效似乎无明显影响。

BACKGROUND ＆ OBJECTIVE： Anti-epidermal growth factor receptor （EGFR） monoclonal antibodies are easily to produce human antimurine antibody response at present clinical use. This may influence therapeutic effect. This study was to evaluate the short-term and long-term efficacy and toxicity of the humanized anti-EGFR monoclonal antibody h-R3 in combination with radiotherapy for Iocoregionally advanced nasopharyngeal carcinoma （NPC）. METHODS： Patients with newly diagnosed stage Ⅲ-Ⅳb （UICC 1997） NPC, who had moderate or strong EGFR expression, were randomized into radiotherapy alone group or radiotherapy combined h-R3 group. Similar dosage and technique of radiotherapy was administered in both groups. The combination group received weekly intravenous infusion of 100 mg h-R3 during radiotherapy. The short-term efficacy was evaluated according to WHO criteria. The survival was analyzed by Kaplan-Meier method. RESULTS： A total of 35 patients were enrolled, 17 in radiotherapy alone group and 18 in combination group. During treatment, only 1 patient withdrew from the combination group. The overall complete remission （CR） rates at the end of treatment, 5 and 17 weeks after treatment were significantly higher in combination group than in radiotherapy alone group （72.2% vs. 35.3%, 83.3% vs. 41.2%, and 83.3% vs. 47.1%, P〈0.05）. Median follow-up time was 31.9 months （range, 4.2-40.7 months）. No significant differences in 3-year locoregional control, distant metastasis-free survival and overall survival rates between the 2 groups were found. Except for 1 patient suffered from grade 2 vomiting, no patient developed other adverse events in combination group. No significant differences in radiotherapy-related adverse events between the 2 groups were observed. CONCLUSIONS： h-R3 is a safe drug which may enhance the response of advanced NPC patients to radiotherapy. However, h-R3 seems not to significantly affect the long-term outcomes.