Effect of acquired cisplatin resistance on the response of a xenografted human hypopharynx carcinoma to concurrent radiochemotherapy with cisplatin.

The optimum integration of chemotherapy and irradiation is of potential clinical significance in the treatment of advanced head and neck carcinomas. In the present study, the interaction of cis-diamminedichloroplatinum(II) (cisplatin) with fractionated radiotherapy was investigated in a human hypopharynx carcinoma and a cisplatin-resistant subline of this tumor, both growing in athymic mice. Two radiochemotherapy schedules which tested single as well as combined-modality treatments were applied. After therapy, the tumor sizes were measured three times per week in order to determine growth delay and treatment:control (T/C) ratios. The results revealed approximately additive effects of both agents in the parent hypopharynx carcinoma. In the resistant subline, such an interaction did not appear after treatment with any of the investigated schedules. However, a significant cross-resistance between cisplatin and radiation was detectable. It can be concluded that multiple courses of a platinum-based induction chemotherapy may be disadvantageous, since the treated tumors may develop drug resistance which obviously limits the effectiveness of a subsequent combined-modality approach.