DECADOSE EFFECTS OF CISPLATIN ON SQUAMOUS-CELL CARCINOMA OF THE UPPERAERODIGESTIVE TRACT .2. CLINICAL-STUDIES

There is evidence that solid tumors rapidly acquire cellular resistanc e to cisplatin. This resistance is usually mild to moderate and could be circumvented with higher concentrations of drug exposure if ancilla ry methods were available to avoid systemic cytotoxicity. The purpose of this study was to determine whether a tenfold increase in dose (dec adose) would overcome cisplatin resistance. In a clinical trial, respo nse effects of cisplatin at dose intensities ranging from 32.5 to 200 mg/m(2) per week, which were delivered by highly selective intraarteri al infusions with a simultaneously administered intravenous neutralizi ng agent, were measured in 31 patients with squamous cell carcinoma (S CC) of the upper aerodigestive tract (UADT). The overall response rate (complete response [CR] and partial response [PR]) to cisplatin thera py at dose intensity intervals of 0 to 74, 75 to 149, and 150 to 200 m g/m(2) per week were 45.5%, 72.7%, and 100%, respectively, The average received dose intensities for nonresponders and responders (CR and PR ) were 57.8 and 120.7 mg/m(2) per week, respectively (P = .031). The r esults indicate that resistance to standard doses of cisplatin by SCC of the UADT, both previously untreated and recurrent, can be substanti ally overcome with ''decadose'' cisplatin therapy. Progress toward imp roving survival of patients with head and neck cancer, and possibly ot her site-specific malignancies, may be achieved by incorporating decad ose cisplatin therapy into a multimodality treatment plan.