PACLITAXEL ADMINISTERED OVER 3-H FOLLOWED BY CISPLATIN IN PATIENTS WITH ADVANCED HEAD AND NECK SQUAMOUS-CELL CARCINOMA - A CLINICAL-PHASE-ISTUDY

We have performed a clinical phase I trial of a combination treatment with paclitaxel given as 3-hour infusion and cisplatin to determine th e maximum tolerated dose and the dose-limiting toxicity in patients wi th recurrent or metastatic squamous cell carcinoma of the head and nec k. Treatment was repeated every 21 days. Doses administered ranged fro m 135 mg/m(2) paclitaxel/75 mg/m(2) cisplatin to 250 mg/m(2) paclitaxe l/100 mg/m(2) cisplatin. Twenty-four patients have been entered into t his study. The maximum tolerated dose was determined to be 225-250 mg/ m(2) paclitaxel/100 mg/m(2) cisplatin. The dose-limiting toxicity of t his regimen was myelosuppression (granulocytopenia). Neurosensory and neuromotor toxicity was moderate. However, analyses of threshold elect rotonus studies indicated subclinical neurotoxicity in most patients. One patient receiving 200 mg/m(2) paclitaxel/100 mg/m(2) cisplatin dev eloped grade 3 motor-neurotoxicity. Orthostatic hypotension was observ ed in 8 patients receiving doses of 200 mg/m(2) paclitaxel/100 mg/m(2) cisplatin or higher. Objective responses were observed at paclitaxel 175 mg/m(2)/cisplatin 100 mg/m(2) (n=5; complete response in 1 patient ), paclitaxel 200 mg/m(2)/cisplatin 100 mg/m(2) (n=3; partial response in 3 patients) and at paclitaxel 225 mg/m(2)/cisplatin 100 mg/m(2) (n =8; partial response in 1 patient). Eleven additional patients had sta ble disease. We conclude that paclitaxel administered as a 3-hour infu sion followed by cisplatin is an active regimen in advanced head and n eck cancer and that orthostatic hypotension may be a potentially signi ficant clinical toxicity.