Predictability of chemosensitivity of histoculture drug response assays and status of p53 gene for organ preservation therapy using neoadjuvant chemotherapy in patients with head and neck carcinomas

头颈癌患者新辅助化疗器官保存治疗中组织培养药物反应测定的化疗敏感性和 p53 基因状态的预测

基本信息

批准号：
11671719
负责人：
HASEGAWA Yasuhisa
金额：
$ 1.98万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671719/
关键词：
Chemosensitivity test Head and Neck Cancer CDDP 5FU TS DPD GSTπ HDRA Cisplatin

项目摘要

The future direction of anticancer chemotherapy is toward personalized chemotherapy corresponding to the variability and individuality of cancers. For this, the prediction of chemosensitivity (1, 2) and development of combined chemotherapy (3) are issues that need to be examined, In the present study, therefore, we investigated the sensitivity of histoculture drug response assay (HDRA) and gene expression (RT-PCR) for anticancer agents administered in case of head and neck cancer. 1) Thirty-three patients with head and neck squamous cell carcinoma (HNSCC) received cisplatin(CDDP)/5-FU chemotherapy. The sensitivity of CDDP was assessed at a concentration of 20 μg/ml, and that of 5FU at a concentration of 120 μg/ml. The cut off value of the inhibition rate was 50%. The clinical response rate for the anticancer chemotherapy ill these 33 cases was 51%. All patients were evaluable for the sensitivity of CDDP.The true positive rate was 78%, true negative rate 80%, and total accuracy 79%. Ele … More ven cases were evaluable for the sensitivity of 5FU.The true positive rate was 50%, true negative rate 80%, and total accuracy 64%.The true negative rate was high for both drugs, and HDRA of CDDP and 5FU was useful for the prediction of ineffectual cases. 2) We investigated the correlation between tumor sensitivity to 5FU and mRNA levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), and also between CDDP sensitivity and glutathione S-transferase (GST)-pi mRNA levels, using RT-PCR.The tumor sensitivity to 5FU was significantly correlated with DPD mRNA levels, However, there was no correlation between TS level and 5-FU sensitivity, and CDDP sensitivity was unrelated to GST-pi. The results of this study suggest that the DPD mRNA level is a useful indicator in predicting the antitumor activity of 5-FU in HNSCC.3) With the aim of organ preservation and downstaging, we administered combined chemotherapy (FP)(5FU 600 mg/m2/day, day 1-6, CDDP 80 mg/m2/day, day 7) in 26 cases of oro- and hypopharyngeal cancer as a neoadjuvant chemotherapy. It produced a partial or complete response in 22 cases, for a response rate was 85%. The high response rate and significance in terms of organ preservation of this combined chemotherapy were thus demonstrated. Less

抗癌化疗的未来方向是针对癌症的变异性和个体性进行个体化化疗，因此，化疗敏感性的预测(1, 2)和联合化疗的发展(3)是目前需要研究的问题。因此，我们研究了组织培养药物反应测定 (HDRA) 和基因表达 (RT-PCR) 对头颈癌中施用的抗癌药物的敏感性 1) 33 名头颈鳞状细胞患者。癌（HNSCC）接受顺铂（CDDP）/5-FU化疗的敏感性以20μg/ml的浓度进行评估，5FU以120μg/ml的浓度进行抑制的截止值。 33例患者抗癌化疗的临床有效率为51%，所有患者均可评价CDDP的敏感性。真实阳性率为51%。 78%，真阴性率80%，总准确率79%。可评估5FU的敏感性。真阳性率为50%，真阴性率80%，总准确率64%。两种药物的阴性率都很高，CDDP和5FU的HDRA有助于预测无效病例2)我们研究了肿瘤对5FU的敏感性与5FU的mRNA水平之间的相关性。使用 RT-PCR 检测胸苷酸合酶 (TS) 和二氢嘧啶脱氢酶 (DPD)，以及 CDDP 敏感性和谷胱甘肽 S-转移酶 (GST)-pi mRNA 水平。肿瘤对 5FU 的敏感性与 DPD mRNA 水平显着相关。 TS水平与5-FU敏感性之间没有相关性，CDDP敏感性与GST-pi无关。本研究结果表明DPD mRNA水平是一个有用的指标。预测 5-FU 在 HNSCC 中的抗肿瘤活性。3) 为了保留器官和降期，我们给予联合化疗 (FP)（5FU 600 mg/m2/天，第 1-6 天，CDDP 80 mg/m2/第 7 天）在 26 例口咽癌和下咽癌中作为新辅助化疗，其中 22 例产生了部分或完全缓解，缓解率为85%，从而证明了这种联合化疗的高反应率和在器官保存方面的意义。