Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial
Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial
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DOI：
10.1093/annonc/mdz020
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发表时间：
2019-04-01
影响因子：
50.5
通讯作者：
Xie, C.
中科院分区：
文献类型：
--
作者：
Zhao, C.;Miao, J.;Xie, C.
背景：我们进行了一项II期单臂试验，以评价抗表皮生长因子受体单抗联合顺铂和5-氟尿嘧啶(PF)作为鼻咽癌根治放疗后复发转移一线治疗的疗效和不良反应(AEs)。样本容量的计算采用SIMON最优两阶段设计。所有患者在顺铂(100 mg/m(2)d1)和5-氟尿嘧啶(4g/m(2))静脉滴注的基础上加用尼莫珠单抗(200 Mg)，每3周1次，最多6个周期。主要终点为客观有效率(ORR)。次要终点包括疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)和不良反应(AES)。结果：共纳入35例患者，其中1期13例，2期22例。总的ORR为71.4%(25/35)，DCR为85.7%(30/35)。中位PFS和OS分别为7.0(95%CI 5.8~8.2)个月和16.3(95%CI 11.4~21.3)个月。非计划探索性分析表明，接受>；=2400mgNimotuzumab和>；=4周期PF的患者在ORR、PFS和OS方面优于未接受治疗的患者(88.9%比12.5%，P<；0.001；7.4月比2.7月，P=0.081；17.0比8.0月，P=0.202)。有利亚组包括有肺转移患者[HROS 0.324(95%CI 0.146~0.717，P=0.008)]和无瘤间隔12个月[HROS 0.307(95%CI 0.131~0.724)，P=0.004]，但转移负担无差异。唯一严重的3/4级不良反应是白细胞减少(62.9%)。结论：尼莫单抗-PF联合化疗对复发转移性鼻咽癌具有潜在疗效，且耐受性良好，可作为一线化疗方案。
Background: We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma after radical radiotherapy.Methods: Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m(2) D1) and 5-fluorouracil (4 g/m(2) continuous infusion D1-4) every 3-weekly for a maximum of six cycles. Primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs.Results: A total of 35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) months and 16.3 (95% CI 11.4-21.3) months, respectively. Unplanned exploratory analyses suggest that patients who received >= 2400 mg nimotuzumab and >= 4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% versus 12.5%, P < 0.001; 7.4 versus 2.7 months, P = 0.081; 17.0 versus 8.0 months, P = 0.202). Favourable subgroups included patients with lung metastasis [HROS 0.324 (95% CI 0.146-0.717),P = 0.008] and disease-free interval of >12 months [HROS 0.307 (95% CI 0.131-0.724), P = 0.004], but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%).Conclusion: Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in recurrent metastatic nasopharyngeal carcinoma.