[an error occurred while processing this directive]|[an error occurred while processing this directive]
阿帕替尼联合放化疗治疗晚期头颈部鳞癌的前瞻性研究
李萌萌,李婷婷,蔡丰,张亚军,张献文,刘静景,周育夫,孙谦,汪庚明,陈如君陈欣,查艮兰,江浩
蚌埠医学院第一附属医院肿瘤放疗科,蚌埠 233004
Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma
Li Mengmeng, Li Tingting, Cai Feng, Zhang Yajun, Zhang Xianwen, Liu Jingjing, Zhou Yufu, Sun Qian, Wang Gengming, Chen Rujun, Chen Xin, Zha Genlan, Jiang Hao
Department of Radiation Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
Abstract：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.
. Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma[J]. Chinese Journal of Radiation Oncology, 2022, 31(2): 125-130.
[1] Chow LQM. Head and neck cancer[J]. N Engl J Med, 2020, 382(1):60-72. DOI:10.1056/NEJMra1715715. [2] Pan R, Zhu M, Yu C, et al. Cancer incidence and mortality:A cohort study in China, 2008-2013[J]. Int J Cancer, 2017, 141(7):1315-1323. DOI:10.1002/ijc.30825. [3] Rahman S, Kraljevi-Paveli S, Markova-Car E. Circadian (De) regulation in head and neck squamous cell carcinoma[J]. Int J Mol Sci, 2019, 20(11):2662. DOI:10.3390/ijms20112662. [4] Leemans CR, Snijders P, Brakenhoff RH. The molecular lanDSCApe of head and neck cancer[J]. Nat Rev Cancer, 2018, 18(5):269-282. DOI:10.1038/nrc.2018.11. [5] Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12):2893-2917. DOI:10.1002/ijc.25516. [6] Miao M, Deng G, Luo S, et al. A phase Ⅱ study of apatinib in patients with recurrent epithelial ovarian cancer[J]. Gynecol Oncol, 2018, 148(2):286-290. DOI:10.1016/j.ygyno.2017.12.013. [7] Scott LJ. Correction to:apatinib:a review in advanced gastric cancer and other advanced cancers[J]. Drugs, 2018, 78(7):759. DOI:10.1007/s40265-018-0913-7. [8] Zhu X, Liu M, Lyu J, et al. Good local tumor control but lethal hemorrhage after apatinib treatment for intractable squamous carcinoma of the floor of the mouth:a case report[J]. Onco Targets Ther, 2018, 11:8909-8913. DOI:10.2147/OTT. S180358. [9] Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamouscell carcinoma of the head and neck[J]. N Engl J Med, 2006, 354(6):567-578. DOI:10.1056/NEJMoa053422. [10] Mesía R, Henke M, Fortin A, et al. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1):a randomised, controlled, open-label phase 2 trial[J]. Lancet Oncol, 2015, 16(2):208-220. DOI:10.1016/s1470-2045(14)71198-2. [11] Zheng Y, Yang X, Yan C, et al. Effect of apatinib plus neoadjuvant chemotherapy followed by resection on pathologic response in patients with locally advanced gastric adenocarcinoma:a single-arm, open-label, phase Ⅱ trial[J]. Eur J Cancer, 2020, 130:12-19. DOI:10.1016/j.ejca.2020.02.013. [12] Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase Ⅲ trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction[J]. J Clin Oncol, 2016, 34(13):1448-1454. DOI:10.1200/JCO.2015.63.5995. [13] Xu Y, Huang Z, Lu H, et al. Apatinib in patients with extensive-stage small-cell lung cancer after second-line or third-line chemotherapy:a phase Ⅱ, single-arm, multicentre, prospective study[J]. Br J Cancer, 2019, 121(8):640-646. DOI:10.1038/s41416-019-0583-6. [14] Lan CY, Wang Y, Xiong Y, et al. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC):a phase 2, single-arm, prospective study[J]. Lancet Oncol, 2018, 19(9):1239-1246. DOI:10.1016/s1470-2045(18)30349-8. [15] Chen X, Qiu T, Zhu Y, et al. A single-arm, phase Ⅱ study of apatinib in refractory metastatic colorectal cancer[J]. Oncologist, 2019, 24(7):883-e407. DOI:10.1634/theoncologist.2019-0164. [16] Hu X, Zhang J, Xu B, et al. Multicenter phase Ⅱ study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer[J]. Int J Cancer, 2014, 135(8):1961-1969. DOI:10.1002/ijc.28829. [17] Xie L, Xu J, Sun X, et al. Apatinib for advanced osteosarcoma after failure of standard multimodal therapy:an open label phase Ⅱ clinical trial[J]. Oncologist, 2019, 24(7):e542-e550. DOI:10.1634/theoncologist.2018-0542. [18] Zhu G, Zhang L, Dou S, et al. Apatinib in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck:a single-arm, phase Ⅱ prospective study[J]. Ther Adv Med Oncol, 2021, 13:17588359211013626. DOI:10.1177/17588359211013 626. [19] 罗利琼,童倩,雷希君,等. 甲磺酸阿帕替尼联合替吉奥对晚期头颈部肿瘤患者的疗效与安全性[J]. 中国医药指南,2020,18(29):77-78. DOI:10.15912/j.cnki.gocm. 2020.29.036. Luo LQ, Tong Q, Lei XJ, et al. Efficacy and safety of apatinib mesylate combined with Tegafur in the treatment of patients with advanced head and neck tumors[J]. Guide Chin Med, 2020, 18(29):77-78. DOI:10.15912/j.cnki.gocm.2020.29.036. [20] Hu C, Zhu P, Xia Y, et al. Role of the NRP-1-mediated VEGFR2-independent pathway on radiation sensitivity of non-small cell lung cancer cells[J]. J Cancer Res Clin Oncol, 2018, 144(7):1329-1337. DOI:10.1007/s00432-018-2667-8. [21] 李兰,郎锦义,周鹏程,等. 阿帕替尼治疗晚期进展性头颈部鳞癌的可行性和安全性[J]. 肿瘤,2019,39(12):1011-1018. DOI:10.3781/j.issn.1000-7431.2019.44.588. Li L, Lang JY, Zhou PC, et al. Efficacy and safety of apatinib treatment for advanced progressive head and neck squamous cell carcinoma[J]. Tumor, 2019, 39(12):1011-1018. DOI:10.3781/j.issn.1000-7431.2019.44.588. [22] Meng M, Ye X, Yang X, et al. Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms:three case reports[J]. J Cancer Res Ther, 2019, 15(2):442-446. DOI:10.4103/jcrt. JCRT_894_18. [23] Guigay J, Aupérin A,Fayette J, et al. Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme):a multicentre, open-label, randomised, phase 2 trial[J]. Lancet Oncol, 2021, 22(4):463-475. DOI:10.1016/s1470-2045(20)30755-5. [24] Liu C, Jia Q, Wei H, et al. Apatinib in patients with advanced chordoma:a single-arm, single-centre, phase 2 study[J]. Lancet Oncol, 2020, 21(9):1244-1252. DOI:10.1016/s1470-2045(20)30466-6. [25] 李艺,窦圣金,张霖,等. PD-1 抗体联合抗血管生成靶向治疗在晚期复发转移头颈部肿瘤中的探索研究[J]. 口腔医学研究, 2020, 36(2):158-163. DOI:10.13701/j. cnki. kqyxyj. 2020. 02. 016. Li Y, Dou SJ, Zhang L, et al. Exploration and study of PD-1 antibody combined with anti-angiogenesis targeted therapy in advanced recurrent and metastatic head and neck tumors[J]. J Oral Sci Res, 2020, 36(2):158-163. DOI:10.13701/j.cnki.kqyxyj.2020.02.016.
2022, Vol. 31 
