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

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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