A phase Ⅲ multicenter trial of radiosensitizing effect and safety of sodium glycididazole in thoracic esophegeal squamous carcinoma
QIN Shang-bin*, WANG Ya-di, YANG Jun-quan, WANG Xiao-hu, LI Hai-bin, YANG Zhi-yong, YU Hong, LI Xue-ying, GAO Xian-shu
*Department Of Radiation Oncology, First Hospital, Peking University, Beijing 100034, China Corresponding author:GAO Xian-shu, Email:xsgao777@hotmail.com
Abstract：Objective To evaluate the efficacy and clinical safety of sodium glycididazole (CMNa) in thoracic esophageal squamous carcinoma. Methods From June 1, 2008 to October 13, 2009, 66 pathologically proved thoracic esophageal squamous carcinoma (stage Ⅱa-Ⅲ, stage Ⅳ with metastases only in supraclavicular lymph nodes,by AJCC 6th ed) were randomized into radiotherapy plus CMNa (A) or radiotherapy plus placebo (B) group. Radiotherapy was given by conventional schedule:1.8－2.0 Gy per fraction, 5 times per week to a total dose of 66 Gy/6.6－7.2w. CMNa was given intravenously 800 mg/m2 3 times a week in solution of 100 ml saline within 30 minutes. Radiotherapy was started 30－60 minutes after completion of infusion. Patients of Group B received placebo in saline solution. A total of 66 patients were enrolled (Group A:32;Group B:34), and four patients were unanalyzable, remaining 31 patients in each Group. Baseline factors were balanced. Results Follow-up rate was 97%. Group A vs. Group B:the overall response rate was 93.5% vs. 67.7%(χ2=6.61,P=0.01), 2-year overall survival was 39.9% vs.29.9%(χ2=0.62,P=0.433), 2-year cancer specific survival was 43.1% vs.26.8%(χ2=0.30,P=0.878), and 2-year progression-free survival was 30.1% vs. 27.9%(χ2=0.02,P=0.586). No severe side effects observed. All patients tolerated CMNa infusion well. Conclusions CMNa is tolerable and effective as a hypoxic radiosensitizer, and its combination with radiotherapy can improve short term effect. However, survival is not improved within our follow-up period.
QIN Shang-bin*,WANG Ya-di,YANG Jun-quan et al. A phase Ⅲ multicenter trial of radiosensitizing effect and safety of sodium glycididazole in thoracic esophegeal squamous carcinoma[J]. Chinese Journal of Radiation Oncology, 2012, 21(5): 426-428.
[1] Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal cancer:long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA,1999,281:1623-1627. [2] Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med,1992,326:1593-1598. [3] Toma-Dasu I, Dasu A, Karlsson M. The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumor response to radiation. Phys Med Biol,2004,49:4463-4475. [4] 王永坤,吴克瑾,林清.乏氧与放射敏感性的研究进展.外科理论与实践,2011,16:89-91. [5] 郑秀龙,孟祥顺,赵芳,等.新增敏剂-甘氨双唑钠对体内肿瘤的放射增敏作用.辐射研究与辐射工艺学报,2000,18:90-95. [6] Zeng YC, Wu R, Xu ZG, et al. Safety and radiation-enhancing effect of sodium glycididazole in locoregionally advanced laryngeal cancers previously treated with platinum-containing chemotherapy regimens:a preliminary report. Cancer Radiother,2010,14:59-64. [7] 王培军,孙维凯,王凡,等.甘氨双唑钠对H22肝癌移植小鼠肺转移的影响.中华放射肿瘤学杂志,2007,16:297-300. [8] 刘孟忠,何立儒,卢泰祥,等.甘氨双唑钠对鼻咽癌放疗增敏作用的长期疗效.中华肿瘤杂志,2006,28:932-937. [9] 蔡勇,李东明,孙艳,等.甘氨双唑钠对恶性肿瘤放射增敏的临床研究.中华放射医学与防护杂志,2008,28:260-261. [10] 孙菁,王凤英.甘氨双唑钠对食管癌放射增敏作用的生存分析.中华放射肿瘤学杂志,2006,15:297-300. [11] Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Nat Cancer Inst,2000,92:205-216. [12] 李彩英,刘明,彰俊杰,等.CT食管癌改良T分期与病理对照.中国医学影像技术,2002,18:236-237. [13] Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123(Radiation Therapy Oncology Group 94-05) phase Ⅲ trial of combined-modality therapy for esophageal cancer:high-dose versus standard-dose radiation therapy. J Clin Oncol,2002,20:1167-1174. [14] Conroy T, Yataghene Y, Etienne PL, et al. Phase Ⅱ randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer,2010,103:1349-1355. [15] 孟祥顺,赵芳,李雨,等.甲硝唑氨酸钠(CMNa)对小鼠肿瘤分次照射的增敏作用.辐射研究与辐射工艺学报,1994,12:109-112. [16] 董桂芝,杜朝晖,王卫东,等.注射用甘氨双唑钠对宫颈癌术后放疗后复发放疗增敏作用的临床观察.中华肿瘤防治杂志,2010,17:455-457. [17] 郑秀龙.肿瘤放疗增敏剂的研究与应用概况甘氨双唑钠研究论文集.上海:第二医大学出版社,2001:4-6. [18] 申戈,鲍云华.针剂甘氨双唑钠放射治疗增敏的随机双盲Ⅱ期临床试验.中华放射肿瘤学杂志,2003,12:254-258. [19] 吴双,杨家林,李志琳,等.甘氨双唑钠对鼻咽癌放射治疗的增敏作用.肿瘤防治研究,2006,33:200-201. [20] 王铁君,李英普,王红勇,等.甘氨双唑钠在Ⅲ期非小细胞肺癌三维适形放疗中应用的观察.中华肿瘤防治杂志,2008,15:1342-1344. [21] 程惠华,傅志超,林贵山,等.甘氨双唑钠联合放疗对根治行放疗后复发食管的增敏作用.中华放射肿瘤学杂志,2007,16:341-343. [22] 杨捷,刘孟忠,蔡玲,等.甘氨双唑钠(CM-Na)联合同期放化疗治疗中晚期食管癌的Ⅱ期临床研究.癌症,2008,27:622-626. [23] 梁军,韩春,王凤英,等.注射用甘氨双唑钠在胸段食管鳞癌同步化放疗中增敏作用的多中心、随机双盲的Ⅱ期临床研究.癌症进展,2011,9:699-706. [24] 张红生.甘氨双唑钠联合同步放化疗治疗局部中晚期食管癌临床分析.现代肿瘤医学,2012,20:91-93. [25] 付良青,郭军华,高洪志,等.肿瘤放疗增敏药甘氨双唑钠(CMNa)的Ⅰ期临床药代动力学研究.中国临床药理学杂志,2000,16:187-190. [26] 王晓萍,云松,张新良,等.放疗增敏剂甘氨双唑钠的Ⅱ期临床研究.临床肿瘤学杂志,2003,8:28-32. [27] 蔡玲,刘孟忠,古模发,等.希美纳联合同期放化疗治疗中晚期食管癌的Ⅰ期临床研究.癌症,2005,24:582-586. [28] 刘燕,杨蓉,任燕.肺癌患者放疗前输入甘氨双唑钠致过敏反应 一例报道.肿瘤预防与治疗,2008,21:488.
2012, Vol. 21 
