A PHASE-I REPORT OF PACLITAXEL DOSE-ESCALATION COMBINED WITH A FIXED-DOSE OF CARBOPLATIN IN THE TREATMENT OF HEAD AND NECK-CARCINOMA

BACKGROUND. Standard therapy for advanced head and neck carcinoma is s urgery and radiation, and the subsequent 5-year survival with this tre atment has been less than 50%. New combined modality treatment strateg ies are being tested to improve survival. New chemotherapy combination s are being developed and administered simultaneously with, or sequenc ed with, radiation and surgery. This article reports the Phase I resul ts of administering paclitaxel and carboplatin preoperatively. The aut hors' objective was to develop an outpatient chemotherapy that would d ownstage tumors and allow organ preservation with equal or improved su rvival as compared with standard therapy. METHODS. Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. AU patients had lesions that were measura ble in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days wit h escalating doses of paclitaxel (150-265 mg/m(2)) given as a 3-hour i nfusion immediately preceding carboplatin. Premedication was used to a void acute hypersensitivity reactions. Carboplatin was administered in travenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). RESULTS. The dose-limiting toxic ities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m(2). Neutropenic fever was observed in 30% of patients at a pacli taxel dose of 250-265 mg/m(2). Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. CONCLU SIONS. Toxicity was acceptable. The maximum tolerated dose of paclitax el was 230 mg/m(2) without hematopoietic growth factor, or 250 mg/m(2) with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this c ombination are warranted in the treatment of these carcinomas. (C) 199 7 American Cancer Society.