阿帕替尼联合放化疗治疗晚期头颈部鳞癌的前瞻性研究

Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma

目的研究旨在探索阿帕替尼联合放化疗治疗晚期头颈部鳞癌的有效性和安全性。方法37例患者在同步放化疗期间口服阿帕替尼250 mg/d,直到放疗结束、经影像学评估为完全缓解、不可接受的不良反应或死亡。在所有具有完整基线和安全性数据的患者中评估基线特征、客观反应率(ORR)和不良反应事件。使用Kaplan-Meier法计算无进展生存(PFS)和总生存(OS)率,Cox模型进行预后影响因素分析。结果ORR为85%(95%CI为72%~98%),中位PFS为17.9个月,2年OS率为62%(95%CI为48%~80%)。近期疗效为无效(HR=0.035,95%CI为0.02~0.652,P=0.025)是OS较差的独立影响险因素,近期疗效为无效(HR=0.104,95%CI为0.017~0.633,P=0.014)和淋巴细胞减少(HR=17.539,95%CI为2.040~150.779,P=0.009)是PFS较差的独立影响因素。常见不良反应(>60%)为淋巴细胞减少症(76%)、白细胞减少症(68%)和放射性黏膜损伤(65%)。最常见的治疗相关3级不良事件是淋巴细胞减少症(49%)。结论阿帕替尼联合放化疗对头颈部鳞癌具有显著的抗肿瘤活性,不良反应可控。对于晚期患者,近期疗效和淋巴细胞减少可能是阿帕替尼联合放化疗疗效的预测因子。

Objective To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma(HNSCC).Methods 37 patients orally received apatinib at 250mg/d during concurrent chemoradiotherapy until completion of radiotherapy,complete remission assessed by imaging examination,the onset of unacceptable toxicity or death.Baseline characteristics,Objective response rates(ORR)and adverse events were assessed in all enrolled patients with complete baseline and safety data.Progression-free survival(PFS)and overall survival(OS)were calculated by Kaplan-Meier method.Prognostic factors were statistically identified using Cox regression models.Results The ORR was 85%(95%CI:72%-98%).The median PFS was 17.9 months and the 2-year OS rate was 62%(95%CI:48%-80%).Ineffective short-term efficacy(HR=0.035,995%CI:0.02-0.652,P=0.025)was an independent risk factor for poor OS.In addition,ineffective short-term efficacy(HR=0.104,95%CI:0.017-0.633,P=0.014)and lymphocytopenia(HR=17.539,95%CI:2.040-150.779,P=0.009)were independent risk factors for poor PFS.Common adverse events(>60%)included lymphocytopenia(76%),leukopenia(68%)and irradiation-induced mucosal injury(65%).The most common treatment-associated grade 3 adverse event was lymphopenia(49%).Conclusions Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity.For patients with advanced HNSCC,short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.