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

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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.