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 potentia l clinical significance in the treatment of advanced head and neck car cinomas. In the present study, the interaction of cis-diamminedichloro platinum(II) (cisplatin) with fractionated radiotherapy was investigat ed in a human hypopharynx carcinoma and a cisplatin-resistant subline of this tumor, both growing in athymic mice. Two radiochemotherapy sch edules which tested single as well as combined-modality treatments wer e applied. After therapy, the tumor sizes were measured three times pe r week in order to determine growth delay and treatment:control (T/C) ratios. The results revealed approximately additive effects of both ag ents in the parent hypopharynx carcinoma. In the resistant subline, su ch an interaction did not appear after treatment with any of the inves tigated schedules. However, a significant cross-resistance between cis platin and radiation was detectable. It can be concluded that multiple courses of a platinum-based induction chemotherapy may be disadvantag eous, since the treated tumors may develop drug resistance which obvio usly limits the effectiveness of a subsequent combined-modality approa ch.