Paclitaxel and carboplatin in head and neck cancer.

Surgery and radiation for advanced head and neck cancer are debilitating and associated with poor survival. If outpatient preoperative chemotherapy could be used such that smaller surgical resections are needed, organs might be preserved and patients' quality of life enhanced. Accordingly, we are conducting a phase I trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in previously untreated patients with advanced head and neck cancer. Study goals include identifying the maximum tolerated paclitaxel dose, evaluating response, and enhancing organ preservation. Newly diagnosed patients with stage III/IV head and neck cancer, measurable disease, and Zubrod performance status < or =2 were eligible. Of 33 patients treated thus far, four (12%) had stage III and 29 (88%) stage IV disease. Their median age was 58 years (range, 17 to 76 years). Treatment was repeated at 21-day intervals for two courses. Patients who achieved clinical partial or complete responses (CRs) received a third course of treatment. If patients were found to have a histologic CR at restaging, radiation was substituted for surgery. Carboplatin was dosed by the Calvert formula to an area under the concentration-time curve of 7.5. Cohorts received escalating doses of paclitaxel (150 to 265 mg/m2) over 3 hours until dose-limiting toxicity was encountered. Five patients were treated at 150 mg/m2, three at 170 mg/m2, eight at 200 mg/m2, six at 230 mg/m2, four at 250 mg/m2, and seven at 265 mg/m2. At present, 26 patients are evaluable for primary tumor response. Thus far, we have seen seven CRs (27%) and seven partial responses (27%), for an overall response rate of 54%. Of 25 patients assessable pathologically, seven (28%) had a CR. Grade 3/4 toxicity at paclitaxel 265 mg/m2 included neurosensory toxicity in 17%, mucositis in 17%, neutropenia in 67%, and thrombocytopenia in 17%. We conclude that paclitaxel 230 mg/m2 and carboplatin area under the curve 7.5 can be administered safely to this patient population. The dose-limiting toxicity that occurred at paclitaxel 265 mg/m2 comprised grade 3/4 neutropenia and thrombocytopenia with associated cumulative grade 2 neuropathy. The maximum tolerated dose of paclitaxel with the combination will be between 230 and 265 mg/m2. This combination has activity in head and neck cancer.