A study of drug resistance and predilection of clinical response to chemotherapy (5FU/Cisplatin) in Head and Neck Cancer

头颈癌化疗（5FU/顺铂）的耐药性和临床反应倾向研究

• 批准号: 09671778
• 负责人: HASEGAWA Yasuhisa
• 金额: $ 1.92万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671778/
• 关键词: Chemosensitivity test; Head and Neck Cancer; HDRA; p53; Cisplatin; 5-FU; Paclitaxel; シスプラチン; 5FU; 感受性試験; P53

1. Combined chemotherapy with 5-FU and cisplatin (FP therapy)5-FU (600mg/m^2, dayl-6) and cisplatin (80mg/m^2, day7) was administered to 17 previously untreated patients (pts) with head and neck squamous cell carcinoma (HNSCC) as neoadjuvant chemotherapy and was also administered to 7 recurrent pts with HNSCC.A favorable response (CR or PR) was observed in 50% and a functional larynx was preserved in 38%. FP therapy seemed to be effective for the laryngeal preservation of pts with advanced HNSCC.2. Predictability of a histoculture drug response assay and p53 tumor suppressor gene for chemotherapy of head and neck cancerIn this study, chemosensitivity in vitro and the p53 status of 32 patients who received the FP or weekly PF chemotherapy, were examined and compared with the clinical response to chemotherapy. Specimens were obtained from biopsy material prior to chemotherapy. The p53 status was determined using PCR-SSCP analysis and direct sequencing. and immunohistochemical analysis of the p53 protein. Chemosensitivity was determined based on histoculture drug response assays (HDRA) with MTT end-point.Seven of 32 pts (22%) demonstrated the mutation of p53 gene. The overall correlation rate of p53 mutation to chemotherapy response was 15/32, 47%. In p53 staining. 6 of 20 pts (30%) showed positive. In HDRA, Ii of 20 pts (55%) showed drug sensitivity. When results of 1-IDRA and status of p53 staining were combined, 7 of 8 pts who showed in vitro drug sensitivity and negative p53 staining had clinical response to chemotherapy. Their correlation was significant (p=0.02).Chemosensitivity for cisplatin-resistant tumorThe aim of this study was to investigate the chemosensitivity of cisplatin-resistant tumor to paclitaxel. Twenty-seven specimens were investigated using HDRA.Of 16 specimens, which demonstrated cisplatin-resistance or low sensitivity, 5specimens, 31% were highly sensitive to paclitaxel. Nineteen percent of tumors were sensitive both cisplatin and paclitaxel.

1.对17例初治的头颈部鳞状细胞癌(HNSCC)患者采用5-FU+顺铂(80 mg/mm2，第7天)联合5-FU(600 mg/m~2，d1-6)联合化疗作为新辅助化疗方案，并对7例复发的HNSCC患者进行化疗，有效率(CR或PR)50%，功能喉保留率38%。FP治疗对于晚期HNSCC.2患者的喉部保护似乎是有效的。组织培养药物反应试验和p53抑癌基因对头颈部肿瘤化疗的预测性本研究检测了32例接受FP或每周PF化疗的患者的体外化疗敏感性和P53状态，并与临床疗效进行了比较。标本取自化疗前的活检材料。用聚合酶链式反应-单链构象多态分析和直接测序的方法确定P53基因的状态。P53蛋白的免疫组织化学分析。采用四甲基偶氮唑盐比色法(HDRA)检测化疗药物敏感性，32例中有7例(22%)检测到p53基因突变。P53基因突变与化疗疗效的总相关性为15/32，占47%。P53染色。6/20例(30%)阳性。在HDRA中，有20例(55%)表现为药物敏感。1-IDRA结果与P53染色情况相结合，8例体外药敏而P53染色阴性的患者中，有7例对化疗有临床反应。顺铂耐药肿瘤的化疗敏感性本研究的目的是探讨顺铂耐药肿瘤对紫杉醇的化疗敏感性。用HDRA检测了27例标本，在16例对顺铂耐药或低敏感的标本中，有5例对紫杉醇高度敏感，占31%。19%的肿瘤对顺铂和紫杉醇都敏感。

项目成果

Hasegawa Y: "High predictability of a histoculture drug response assay and p53 staining for chemotherapy of head and neck cancer" Proceeding of the 1st World Congress on HEAD AND NECK ONCOLOGY. 1203-1207 (1998)

Hasekawa Y：“头颈癌化疗的组织培养药物反应测定和 p53 染色的高预测性”第一届世界头颈肿瘤学大会论文集。