VM_(26)+DDP方案同期联合脑放疗治疗支气管肺癌脑转移

VM_(26)+DDP regimen given concurrently with whole-brain radiotherapy for brain metastasis from lung cancinoma

背景与目的：近年来肺癌脑转移的发病率随着支气管肺癌的发病率逐年增加而明显上升，文献报道达30％-50％。放射治疗是治疗脑转移的主要手段，而目前为止化疗与放疗联合治疗脑转移的研究较少。本研究旨在比较支气管肺癌脑转移同步放化疗与单放疗的临床疗效、生存率和毒性反应。方法：自2000年9月至2001年10月将41例支气管肺癌患者随机分组，其中20例进入同步放化疗组，21例进入单放疗组。同步放化疗组中，男性14例，女性6例，平均年龄50岁（范围40—70岁），非小细胞肺癌16例，小细胞癌4例；单放疗组中，男性14例，女性7例，平均年龄52岁（范围40—73岁），非小细胞肺癌19例，小细胞癌2例。同步放化疗组化疗方案：鬼臼噻吩甙（VM26）每天60mg／m^2，d1-3；顺铂（DDP）60mg／m^2，d1；放射治疗从化疗第1天开始，6MV-X线照射，3Gy／次，全脑照射二周总剂量为30Gy／10次。单放疗组：放射治疗方案同同步放化疗组。结果：全组所有患者均按计划完成治疗。同步放化疗组完全缓解率（CR）为25％，部分缓解率（PR）为50％，无变化（SD）为25％。单放疗组CR为4．76％，PR为33．33％，无变化（SD）为61．9％。两组的CR率及有效率（CR＋PR）均有显著性差异（P=0．011，P=0．019）。同步放化疗组的1、2、4年生存率分别为44．44％、33．33％、11．11％，中位生存时间为14月。单放疗组的1、2、4年生存率为31．58％、26．67％、0％，中位生存时间为11月。两组无显著性差异（P=0．2015）。毒副反应：同步放化疗组Ⅲ／Ⅳ度白细胞下降（40％），血小板下降（25％）和胃肠道反应（50％）与单放疗组比（4．76％，0，9．52％），均有显著性差异（P=0．007，P=0．016，P=0．005）。结论：对支气管肺癌脑转移治疗同步放化疗的方案，其近期有效率优于单放疗，并且有提高远期生存率的可能性，虽毒副反应增加，但患者均能耐受。

Background and Purpose： In recent years, along with marked rise in the incidence of lung cancer, the incidence of brain metastasis from lung cancer has increased year by year. The main treatment strategy of lung cancer with brain metastasis is irradiation, while so far there are only few researches concerning chemotherapy combined with radiotherapy for these patients. The aim of this study is to evaluate the therapeutic effect, survival rate and toxicity of chemotherapy with VM26 ＋ DDP regimen given concurrently with whole-brain radiotherapy in lung cancer with brain metastasis. Methods： From Sep. 2000 to Oct. 2001, forty-one patients with lung eaneer with brain metastasis were divided randomly into two groups： 20 patients（ 14 male, 6 female） received eoncurrent chemoradiotherapy （ chemoradiotherapy group）, the other 21 patients（ 14 male, 7 female） received only radiotherapy（ radiotherapy group）. In the ehemoradiotherapy group, the average age was 50 years with range 40 to 70 years, 16 patients were non-small-cell lung cancer, 4 patients were small-cell lung cancer. In the radiotherapy group, the average age was 52 years with range 40 to 73 years and 19 patients were non-small- cell lung cancer, 2 patients were small-cell lung cancer. For both groups, the same radiation technique was given with conventional fraction. Radiotherapy was delivered by 6MV. Fraetionations of 3Gy/fraction/day was delivered 10Gy/5 factions/ week. The total dose was 30Gy/10Fr/2W. For chemoradiotherapy group, the patients were also given concurrent chemotherapy （ VM26 60mg/m^2/day iv on days 1-3, cisplatin 60 mg/m^2 iv on the 1^st day）. Results： The response rate and complete response in the chemoradiotherapy group was significantly higher than that in the radiotherapy group（75% v？ 38.10%, P 〈0.05 and 25% vs 4.76%, P 〈0.05）. Among 20 patients assessable for response in the ehemoradiotherapy group, 15 （75%） of 20 responded, including five （25%） patients with a complete response and 10 （50%） patientswith a partial response. With radiotherapy alone, 8 （ 38. 10%） of 21 assessable patients responded, including one （4.76%） complete responses and seven （33.3%） partial responses. The 1-, 2- and 4-year survival rates in the chemoradiotherapy group was 44.44%, 33.33%, 11.11%. With radiotherapy group was 31.58%, 26.67%, 0%. The 1-, 2- and 4- year survival rates in the chemoradiotherapy group were statiscally similar to those in the radiotherapy group （ X^2 = 1.63, P =0. 2015）. The median time in the chemoradiotherapy group was 14 months. The median time in the radiotherapy group was 11 months. The acute toxic effect of grade Ⅲ/Ⅳ myelotoxicity, nausea/vomiting in the chemoradiotherapy group（ leucocyte 40%, blood platelet 25%, nausea/vomiting 50%）were significantly higher than those in the radiotherapy group （leucocyte 4.76% , blood platelet 0, nausea/vomiting 9.52% ） （ P 〈0. 05）. Conclusions： Chemotherapy combined with wholebrain radiotherapy can be safely performed for lung cancer with brain metastasis and its short-term response is quite satisfactory. It can also increase the acute toxic effect, but all patients can tolerate this treatment regimen. It may be worthy of further clinical investigation.