摘要
背景与目的:个体化化疗是脑胶质瘤重要的辅助治疗方法之一,本研究应用四氮唑盐比色法(methyl thiazolyl tetrazolium,MTT)检测脑胶质瘤细胞体外对化疗药物的敏感性,为胶质瘤的个体化化疗提供参考,并根据药敏结果采用替尼泊苷(VM-26)与尼莫司汀(ACNU)分别联合顺铂(CDDP)进行胶质瘤的化疗,评价其疗效。方法:39例胶质瘤进行原代细胞培养,采用MTT法检测胶质瘤对常用八种化疗药物的敏感性,并根据试验结果将患者分为两组进行化疗(VM26-CDDP组和ACNU-CDDP组),按WHO实体瘤疗效评价标准评价疗效。结果:39例患者中37例获得检测结果,体外培养成功率达94.9%。37例胶质瘤细胞体外对八种化疗药物的敏感性从高到低依次为:VM-26>ACNU>Taxol>TMZ>CDDP>BCNU>VCR>Fotemustine。胶质瘤的病理级别及初发、复发对药物敏感性无显著性影响。35例患者接受化疗,共进行119个周期的化疗,ACNU组58个周期,VM-26组61个周期。其中无完全缓解(complete response,CR)病例,VM-26组部分缓解(partial response,PR)1例(5.6%),稳定(stable disease,SD)14例(77.8%),进展(progressive disease,PD)3例(16.6%),客观有效率(CR+PR)为5.6%,疾病控制率(CR+PR+SD)为83.4%;ACNU组部分缓解1例(5.9%),稳定(SD)14例(82.3%),进展2例(11.1%),客观有效率为5.9%,疾病控制率为88.2%。VM-26组患者中位无进展生存期(PFS)Ⅱ级为10.60个月(95%CI:7.21-15.46),Ⅲ、Ⅳ级为3.2个月(95%CI:2.3-5.20),中位总生存(OS)Ⅱ级为13.33个月(95%CI:10.21-16.46),Ⅲ、Ⅳ级为7.29个月(95%CI:4.92-9.65);ACNU组中位无进展生存期(PFS)Ⅱ级为9.70个月(95%CI:7.23-14.77),Ⅲ、Ⅳ级为3.5个月(95%CI:2.24-5.06),中位总生存(OS)Ⅱ级为14.09个月(95%Cl:10.88-16.12),Ⅲ、Ⅳ级为6.20个月(95%Cl:5.94-8.49)。结论:MTT检测可以作为胶质瘤体外药实试验的一种方法,MTT体外药敏实验对排除无效药物、筛选敏感药物,提高胶质瘤的化疗效果,具有一定的参考价值。根据药敏结果选择VM-26和ACNU联合CDDP化疗可取得较好的总反应率和疾病控制率。
BACKGROUND ＆ OBJECTIVE： Individualized chemotherapy is one of the important treatments for glioma patients. The present study was to examine in vitro chemo-sensifivity with MTT assay and evaluate the effectiveness of the regimen of cisplatin （CDDP） combined with teniposide or nimustine （ACNU） . METHODS： The fresh glioma cells derived from 39 glioma patients were cultured in vitro. The sensitivity of cultured glioma cells to eight chemotherapeutic drugs was determined by utilizing MTT colorimetric assay. VM26CDDP group and ACNU-CDDP group were divided according to the drug sensitivity. The clinical effectiveness was evaluated according to Response Evaluation Criteria in Solid Tumors （RECIST）. RESULT：MTT assay was performed for 39 glioma specimens and succeeded in 37cases. The success rate was 94.9%. In 37 cases, the sensitivity sequence of eight chemotherapeutic drags from high to low was VM-26 〉ACNU 〉Taxol 〉TMZ 〉CDDP 〉BCNU 〉VCR 〉 Fotemustine. There was no significant difference of pathological grade and newly-diagnosed or relapse of the tumor on chemo-sensitivity of the patientr Thirty-five patients received a total of 119 cycles of chemotherapy （58 cycles in ACNU group, 61 cycles in VM-26 group）. No complete response （CR） was achieved. The rate of partial response （PR）, stable disease （SD） and progressive disease （PD） were found in 1 patient （5.6%）, 14 cases （77.8%）,3 cases （16.6%）, in VM26 group, respectively. Meanwhile, Objective Efficiency （CR＋PR） and disease control rate （CR＋PR＋SD） were 5.6% and 83.4%, respectively. In ACNU group, 1 patients （5.9%） showed PD, 14 patients （82.3%） had SD and 2 patients （11.1%） were PD. The CR＋PR and CR＋PR＋SD were 5.9% and 88.2%, respectively. Median progression-free survival （PFS） in VM26 group was 10.60 months （95%CI： 7.21-15.46） for grade Ⅱ and 3.2 months （95%CI： 2.3-5.20） for grade Ⅲ/Ⅳ, respectively. Median overall survival （OS） was 13.33 months （95%Ck 10.21-16.46） for grade Ⅱ and 7.29 months （95%CI： 492-9.65） for grade Ⅲ/Ⅳ, respectively. In ACNU group, PFS for grade Ⅱ and grade Ⅲ/Ⅳ was 9.70 months （95%CI： 723-14.77） and 3.5 months （95%CI： 2.24-5.06）, respectively. And the OS was 14.09 months （95%CI： 10.88-16.12）for grade Ⅱ and 6.20 months for grade Ⅲ/Ⅳ （95%CI： 5.94-8.4）, respectively. CONCLUSIONS： MTT assay is one of the methods for determining sensitivity of chemotherapeutic agents in vitro. It may provide useful information to avoid ineffective chemotherapy and identify efficient agent for glioma chemotherapy. The combined regimen of CDDP with ACNU or VM-26 may improve overall response rate, disease control rate according to drug sensitivity.
出处
《中国神经肿瘤杂志》
2009年第4期254-259,共6页
Chinese Journal of Neuro-Oncology
