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

1. 5-FU +顺铂联合化疗（FP治疗）5-FU (600mg/m^2, day -6) +顺铂（80mg/m^2, day - 7）作为新辅助化疗治疗17例既往未治疗的头颈部鳞状细胞癌（HNSCC）患者，7例复发的HNSCC患者也给予5-FU +顺铂联合化疗。50%的患者出现了良好的反应（CR或PR）， 38%的患者保留了喉部功能。FP治疗对于晚期hnsct患者的喉保存似乎是有效的。组织培养药物反应试验和p53肿瘤抑制基因对头颈部肿瘤化疗的可预测性在本研究中，对32例接受FP或每周PF化疗的患者的体外化疗敏感性和p53状态进行了检查，并与化疗的临床反应进行了比较。化疗前从活检材料中获得标本。采用PCR-SSCP分析和直接测序确定p53状态。以及p53蛋白免疫组化分析。化疗敏感性是基于MTT终点的组织培养药物反应试验（HDRA）来确定的。32例患者中有7例（22%）表现出p53基因突变。p53突变与化疗反应的总体相关率为15/ 32,47 %。p53染色。20例PTS中6例（30%）呈阳性。在HDRA中，20例患者中有2例（55%）出现药物敏感。结合1-IDRA结果和p53染色情况，8例体外药物敏感且p53染色阴性的患者中有7例对化疗有临床反应。相关性有统计学意义（p=0.02）。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。采用HDRA对27个标本进行了调查。顺铂耐药或低敏感16例，紫杉醇高敏感5例，占31%。19%的肿瘤对顺铂和紫杉醇均敏感。

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.