沙利度胺联合放疗治疗食管癌的临床观察

Clinical effect observation of VEGF expression interfered by Thalidomide combined with radiotherapy in esophageal cancer treatment

目的前瞻性研究沙利度胺干预下食管癌患者放疗过程中血清血管内皮生长因子（VEGF）水平的动态变化及近期疗效和耐受性。方法采集86例食管癌患者放疗前、中、后的血清，应用酶联免疫吸附法（ELISA）测定血清VEGF水平，根据患者放疗中VEGF水平的变化给予沙利度胺干预，将83例（另外3例因不耐受放疗而中断治疗）患者分成服药组32例（放疗中VEGF水平升高或不变的患者给予口服沙利度胺至放疗结束）和未服药组51例（VEGF水平降低的患者不服用沙利度胺放疗至结束），观察沙利度胺干预下食管癌放疗的疗效及服用药物的安全性。另设30例健康对照组。结果86例食管癌患者放疗前血清VEGF表达水平较30例健康对照者升高，差异有统计学意义（t=5．07，P〈0．01），且与原发肿瘤大小（t=4．55，P〈0．01）、淋巴结转移（t=7．50，P〈0．01）、组织病理类型（F=3．40，P〈0．01）及临床分期均有关（t=2．52，P〈0．01），而与病变部位、远处转移、x射线分型、患者性别、年龄均无关（P均〉0．05）。服药组患者放疗后较放疗中血清VEGF的表达水平降低（t：2．37，P〈0．05），放疗有效率为71．88％；未服药组患者放疗中、后血清VEGF的表达水平差异无统计学意义（t=0．18，P〉0．05），服药组与未服药组的患者比较，头晕、倦怠反应的发生率分别为62．50％和15．69％（X2=19．28，P=0．000），嗜睡的发生率分别为18．75％和1．96％（X2=5．168，P=0．023），Ⅲ～Ⅳ度食管炎发生率分别为12．50％和11．76％（X2=0．061，P=0．806），Ⅲ～Ⅳ度白细胞下降发生率分别为6．25％和9．80％（X2=0．026，P=0．872），Ⅲ～Ⅳ度血小板下降发生率分别为3．13％和5．88％（X2=0．002，P=0．965），Ⅲ～Ⅳ度恶心呕吐发生率分别为9．38％和27．45％（X2=2．913，P=0．088），过敏反应的发生率均为0。结论沙利度胺能够降低食管癌患者血清VEGF的表达水平，患者服用沙利度胺后耐受性较好。

Objective To prospectively study the dynamic variation of vascular endothelial growth factor （VEGF） , the short-term efficiency and the tolerability of the esophageal cancer patients treated by radiotherapy combined with thalidomide. Methods The serum samples of 86 esophageal cancer patients were collected before, during and after the radiotherapy. The VEGF levels were assayed by enzyme-linked immunosorbent assay （ELISA）. 3 patients interrupted the treatment because of intolerance radiotherapy. Based on the changes of VEGF level, 32 esophageal cancer cases whose VEGF levels increased or remained were assigned to the group to which thalidomide was given during the whole course of radiotherapy. The rest 51 patients whose VEGF level decreased received radiotherapy without thalidomide during the whole course. In addition, 30 healthy cases were included in control group. Then the efficiency and safety of the introduction of thalidomide in radiotherapy were investigated. Results The VEGF levels of 86 esophageal cancer cases were significantly higher than the 30 healthy control cases （ t = 5.07, P 〈 0. 01 ）, which were also correlated with the primary tumor size （ t = 4.55, P 〈 0. 01 ） , lymph node metastasis （ t = 7.50, P 〈 0. 01 ） , histological type（ F = 3.40, P 〈 0. 01 ） and clinical stage （ t = 2.52, P 〈 0. 01 ）. However, it was irrelevant to the lesion site, distant metastasis, X-ray pathologic type, gender or age （P 〉 0. 05）. For thethalidomide involved group, the VEGF level after radiotherapy was significantly lower than during radiotherapy （ t = 2.37, P 〈 0. 05 ） with an effective rate of 71.88%. For the rest 51 cases without using thalidomide, the effective rate was 78.43% yet there was no significant difference between the VEGF levels during and after radiotherapy （t=0.18, P 〉 0.05）. 62.50% patients reported symptoms of dizzy and burnout after using thalidomide, while this incidence was 15.69% for the rest patients （X2 = 19.28,P = 0. 000）. For the groups with or without thalidomide combination, the sleepiness incidences were 18.75% and 1.96% , respectively （,v2 = 5. 168, P = 0. 023 ） ; the Ⅲ - Ⅳ grade esophagitis incidences were 12. 50% and 11.76% , respectively （X2 = 0. 061, P = 0. 806） ; the Ⅲ- IV grade leukocyte decrease incidences were 6. 25% and 9.80% , respectively （X2 = 0. 026, P = 0. 872） ; the Ⅲ - IV grade platelet descend incidences were 3.13% and 5.88% , respectively （X2 = 0. 002, P = 0. 965 ） ; the Ⅲ - IV grade nausea and vomiting incidences were 9.38% and 27.45% , respectively （X2 = 2. 913, P = 0. 088 ）. No anaphylaxis was observed. Conclusions Thalidomide can decrease the VEGF expression level of esophazeal cancer patients. Patients treated with thalidomide show good tolerance and compliance.