Molecular targets of 5FU and combined chemotherapy of 5FU plus low dose CDDP for head and neck cancer

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We examined the factors regulating effectiveness of anti-cancer agents especially, 5FU and CDDP, for the purpose of establishing of order-made cancer chemotherapy that will improve prognosis and QOL.Materials and methods : 1) For organ preservation, we administered neoadjuvant 5FU and CDDP chemotherapy (FP) to head and neck cancer patients. 2) We conducted in vitro chemosensitivity tests using histoculture drug response assay (HDRA) on surgical specimens, and performed real-time RT-PCR for the quantitative detection of expression levels of mRNA that may regulate anti-cancer agents. We then analyzed the correlation between them.Results : 1) Among 13 untreated head and neck cancer patients who underwent FP therapy, 10 patients (77%) achieved PR or above. 2) Along with the elevation of HER-2 mRNA expression levels, there was a downward tendency in the inhibition index for 5FU and CDDP in surgical specimens, and we detected a significant upward tendency in HER-2 mRNA expression levels among non-responders of HDRA to 5FU and CDDP.On the other hand, the 5FU inhibition index rose with elevations in COX-2 mRNA expression levels, although the significance of this is unclear. This should be investigated in the future with a greater number of patients.Conclusion : There is a need to analyze the enzyme activity and quantitatively detect expression levels of mRNA for factors relating to metabolism of 5FU. Furthermore, detecting the molecular marker that represents the tumor characteristics in individual patients, we hope to establish order-made cancer chemotherapy that will allow us to select the best regimen for patients through clinical trials. We also hope to apply detection and selection cDNA array to the molecular marker.