Basic and clinical studies on an overcome of drug resistance inchemotherapy for heas and neck cancer

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(1) Basic research : The expression of P-glycoprotein(P-gp) which participates in drug resistance was immunohistochemically examined in 25 cases of malignant tumors of the head and neck. As a result, the expression of P-gp was observed in one case of malignant fibrous hitiocytoma after chemotherapy. And again the expression of P-gp was found in 4 out of 5 cases of adenoid cystic carcinoma even before chemotherapy, which may explain a possibility of natural resistance in these tumors. These facts that P-gp was expressed in some malignant tumors of the head and neck may suggest a correlation between P-gp and drug sensitivity.Then we studied the expression of mdrl at the level of mRNA.The methods used are slot blot hydridization, Northern blot hybridization, and in situ hybridization. The expression of mdr1mRNA was recognized in ISH and RT-PCR even in cases not observed in Northern blot and slot blot hybridization. In some cases, the expression of mdr1mRNA did not coincide with the results of the expression which were shown in immunostain of P-gp.(2) Clinical research : A newly developped regimen consisits of cisplatin(CDDP), etoposide(VP-16), and mitomycin C(MMC). Administration method is as follows : CDD P 60mg/m^2 iv over 2 hours on day 1, VP-16 40mg/m^2 iv over 1 hour on days 1-3, MMC 7mg/m^2 iv bolus on day 1. Complete response was achieved in one case of recurrent laryngeal cancer, although he received VMP therapy (VCR+MTX+REP), CDDP+VP-16, radiotherapy and radical surgery with reconstruction. Biosy was negative after chemotherapy. This result was very encouraging. We will try concurrent chemotherapy and radiotherapy in near future.