EGFR单抗联合化疗治疗245例晚期头颈鳞癌疗效分析
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摘要
目的:评价表皮生长因子受体(EGFR)单抗(泰欣生)治疗晚期头颈部鳞癌的有效性和安全性。方法:选取上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科2008年5月—2017年12月收治的245例晚期(Ⅲ-Ⅳ期)头颈鳞癌患者作为研究对象,分为原发组与复发组,其中原发组152例,复发组93例。原发组和复发组治疗方案均为以铂类为主的化疗联合EGFR单抗100～200 mg/次静滴,分析2组患者的用药安全性和有效性。采用SPSS 17.0软件包对数据进行统计学分析。结果:治疗后,原发组42例口咽癌患者总有效率为81.0%,110例口腔癌患者总有效率为45.4%;复发组9例口咽癌患者总有效率为44.4%,84例口腔癌患者总有效率为27.4%。原发组中位生存期为57个月,复发组中位生存期为8个月;治疗5年后,原发组总生存率为47.7%,复发组总生存率为8.0%。皮疹为EGFR单抗主要不良反应,但发生率仅为1.63%。结论:EGFR单抗联合以铂类为主的化疗对晚期头颈部鳞癌比单纯化疗有更高的有效率和生存率,且止痛效果显著,为手术等后续治疗创造了更好的条件,并可有效改善患者的生活质量,未增加严重化疗不良反应,安全性良好,具有很高的临床推广应用价值。
PURPOSE: To study the efficacy and safety of epidermal growth factor receptor(EGFR) monoclonal antibody in the treatment of advanced head and neck squamous cell carcinoma. METHODS: Two hundred and forty-five patients with advanced(stage III-IV) head and neck squamous cell carcinoma were selected from May 2008 to December 2017.They were divided into primary group(n =152) and relapse group(n =93). Both groups received platinum-based chemotherapy combined with EGFR monoclonal antibody 100-200 mg per intravenous drip. The safety and efficacy of the treatment were analyzed. SPSS 17.0 software package was used for statistical analysis. RESULTS: After treatment, the total effective rate was 81.0% in 42 patients with primary oropharyngeal cancer and 45.4% in 110 patients with primary oral cancer, 44.4% in 9 patients with recurrent oropharyngeal cancer and 27.4% in 84 patients with recurrent oral cancer.The median survival time was 57 months in the primary group and 8 months in the relapse group. After five years of treatment, the overall survival rate was 47.7% in the primary group and 8.0% in the relapse group. Skin rash was the main side effect of EGFR mAb, but the incidence was only 1.63%. CONCLUSIONS: EGFR monoclonal antibody combined with platinum-based chemotherapy for advanced head and neck squamous cell carcinoma has a higher effective rate and survival rate than chemotherapy alone, and the analgesic effect is remarkable, which creates a better treatment opportunity for subsequent treatment such as surgery, and can effectively improve the quality of life of patients, and does not increase serious adverse reactions of chemotherapy.
PURPOSE: To study the efficacy and safety of epidermal growth factor receptor(EGFR) monoclonal antibody in the treatment of advanced head and neck squamous cell carcinoma. METHODS: Two hundred and forty-five patients with advanced(stage III-IV) head and neck squamous cell carcinoma were selected from May 2008 to December 2017.They were divided into primary group(n =152) and relapse group(n =93). Both groups received platinum-based chemotherapy combined with EGFR monoclonal antibody 100-200 mg per intravenous drip. The safety and efficacy of the treatment were analyzed. SPSS 17.0 software package was used for statistical analysis. RESULTS: After treatment, the total effective rate was 81.0% in 42 patients with primary oropharyngeal cancer and 45.4% in 110 patients with primary oral cancer, 44.4% in 9 patients with recurrent oropharyngeal cancer and 27.4% in 84 patients with recurrent oral cancer.The median survival time was 57 months in the primary group and 8 months in the relapse group. After five years of treatment, the overall survival rate was 47.7% in the primary group and 8.0% in the relapse group. Skin rash was the main side effect of EGFR mAb, but the incidence was only 1.63%. CONCLUSIONS: EGFR monoclonal antibody combined with platinum-based chemotherapy for advanced head and neck squamous cell carcinoma has a higher effective rate and survival rate than chemotherapy alone, and the analgesic effect is remarkable, which creates a better treatment opportunity for subsequent treatment such as surgery, and can effectively improve the quality of life of patients, and does not increase serious adverse reactions of chemotherapy.
引文
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[14] Lamont EB, Vokes EE. Chemotherapy in the management of squamous-cell carcinoma of the head and neck[J]. Lancet Oncol,2001, 2(5):261-269.
[15] Rodríguez MO, Rivero TC, del Castillo Bahi R, et al.Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck[J]. Cancer Biol Ther, 2010, 9(5):343-349.
[16] Cohen EE. Role of epidermal growth factor receptor pathwaytargeted therapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck[J]. J Clin Oncol,2006, 24(17):2659-2665.
[17] Kameswaran M, Samuel G, Dev Sarma H, et al.131INimotuzumab-A potential radioimmunotherapeutic agent in treatment of tumors expressing EGFR[J]. Appl Radiat Isot, 2015,102:98-102.
[18] Vermorken JB, Specenier P. Optimal treatment for recurrent/metastatic head and neck cancer[J]. Ann Oncol, 2010, 21(Suppl 7):252-261.
[19] Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck[J].N Engl J Med, 2006, 354(6):567-578.
[20] Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer[J]. N Engl J Med, 2008, 359(11):1116-1127.
[21] Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled,multicenter phaseⅡstudy to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy[J]. J Clin Oncol,2007, 25(16):2171-2177.
[22] Sundvall M, Karrila A, Nordberg J, et al. EGFR targeting drugs in the treatment of head and neck squamous cell carcinoma[J].Expert Opin Emerg Drugs, 2010, 15(2):185-201.
[23] Basavaraj C, Sierra P, Shivu J, et al. Nimotuzumab with chemoradiation confers a survival advantage in treatment-na?ve head and neck tumors over expressing EGFR[J]. Cancer Biol Ther, 2010, 10(7):673-681.
[24] Xu S, Ramos-Suzarte M, Bai X, et al. Treatment outcome of nimotuzumab plus chemotherapy in advanced cancer patients:a single institute experience[J]. Oncotarget, 2016, 7(22):33391-33407.
[25] Ledón N, CasacóA, Casanova E, et al. Comparative analysis of binding affinities to epidermal growth factor receptor of monoclonal antibodies nimotuzumab and cetuximab using different experimental animal models[J]. Placenta, 2011, 32(7):531-534.
[26] Rojo F, Gracias E, Villena N, et al. Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck:a SENDO Foundation study[J]. Clin Cancer Res,2010, 16(8):2474-2482.
[2] Mountzios G. Optimal management of the elderly patient with head and neck cancer:Issues regarding surgery, irradiation and chemotherapy[J]. World J Clin Oncol, 2015, 6(1):7-15.
[3] Spector JG, Sessions DG, Chao KS, et al. Management of stageⅡ(T2N0M0)glottic carcinoma by radiotherapy and conservation surgery[J]. Head Neck, 1999, 21(2):116-123.
[4] Sessions DG, Lenox J, Spector GJ. Supraglottic laryngeal cancer:analysis of treatment results[J]. Laryngoscope, 2010, 115(8):1402-1410.
[5] Seiwert TY, Cohen EE. State-of-the-art management of locally advanced head and neck cancer[J]. Br J Cancer, 2005, 92(8):1341-1348.
[6] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013[J]. CA Cancer J Clin, 2013, 63(1):11-30.
[7] Posner MR, Haddad RI, Wirth L, et al. Induction chemotherapy in locally advanced squamous cell cancer of the head and neck:evolution of the sequential treatment approach[J]. Semin Oncol,2004, 31(6):778-785.
[8] Lefebvre JL, Chevalier D, Luboinski B, et al. Larynx preservation in pyriform sinus cancer:preliminary results of a european organization for research and treatment of cancer phaseⅢtrial[J].J Natl Cancer Inst, 1996, 88(13):890-899.
[9]郭伟.晚期口腔颌面-头颈部鳞癌靶向治疗的进展浅析[J].口腔颌面外科杂志, 2012, 22(2):77-81.
[10] Busch CJ, Tribius S, Schafhausen P, et al. The current role of systemic chemotherapy in the primary treatment of head and neck cancer[J]. Cancer Treat Rev, 2015, 41(3):217-221.
[11] Zhong LP, Zhang CP, Ren GX, et al. Randomized phaseⅢtrial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma[J]. J Clin Oncol, 2013, 31(6):744-751.
[12] Mathers CD, Shibuya K, Boschi-Pinto C et al. Global and regional estimates of cancer mortality and incidence by site:I.Application of regional cancer survival model to estimate cancer mortality distribution by site[J]. BMC Cancer, 2002, 2:36.
[13] Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics,2002[J]. CA A Cancer J Clin, 2005, 55(2):74-108.
[14] Lamont EB, Vokes EE. Chemotherapy in the management of squamous-cell carcinoma of the head and neck[J]. Lancet Oncol,2001, 2(5):261-269.
[15] Rodríguez MO, Rivero TC, del Castillo Bahi R, et al.Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck[J]. Cancer Biol Ther, 2010, 9(5):343-349.
[16] Cohen EE. Role of epidermal growth factor receptor pathwaytargeted therapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck[J]. J Clin Oncol,2006, 24(17):2659-2665.
[17] Kameswaran M, Samuel G, Dev Sarma H, et al.131INimotuzumab-A potential radioimmunotherapeutic agent in treatment of tumors expressing EGFR[J]. Appl Radiat Isot, 2015,102:98-102.
[18] Vermorken JB, Specenier P. Optimal treatment for recurrent/metastatic head and neck cancer[J]. Ann Oncol, 2010, 21(Suppl 7):252-261.
[19] Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck[J].N Engl J Med, 2006, 354(6):567-578.
[20] Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer[J]. N Engl J Med, 2008, 359(11):1116-1127.
[21] Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled,multicenter phaseⅡstudy to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy[J]. J Clin Oncol,2007, 25(16):2171-2177.
[22] Sundvall M, Karrila A, Nordberg J, et al. EGFR targeting drugs in the treatment of head and neck squamous cell carcinoma[J].Expert Opin Emerg Drugs, 2010, 15(2):185-201.
[23] Basavaraj C, Sierra P, Shivu J, et al. Nimotuzumab with chemoradiation confers a survival advantage in treatment-na?ve head and neck tumors over expressing EGFR[J]. Cancer Biol Ther, 2010, 10(7):673-681.
[24] Xu S, Ramos-Suzarte M, Bai X, et al. Treatment outcome of nimotuzumab plus chemotherapy in advanced cancer patients:a single institute experience[J]. Oncotarget, 2016, 7(22):33391-33407.
[25] Ledón N, CasacóA, Casanova E, et al. Comparative analysis of binding affinities to epidermal growth factor receptor of monoclonal antibodies nimotuzumab and cetuximab using different experimental animal models[J]. Placenta, 2011, 32(7):531-534.
[26] Rojo F, Gracias E, Villena N, et al. Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck:a SENDO Foundation study[J]. Clin Cancer Res,2010, 16(8):2474-2482.