Multicenter phase I-II trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy for patients with locally advanced squamous cell cancerof the head and neck

Purpose: We conducted a phase I-II, multi-institutional trial to determine the maximum-tolerated dose (MTD) of cisplatin in an induction chemotherapy regimen of docetaxel, cisplatin, and fluorouracil for squamous cell cancer of the head and neck (SCCHN) and to determine the safety, tolerability, and efficacy of the regimen at MTD. Patients and Methods: A total of 43 patients with previously untreated, loc ally advanced, curable SCCHN were entered. Overall, 29 patients (67%) had N 2 or N3 nodal disease and nine (21%) had T4 primary tumors. All patients re ceived docetaxel 75 mg/m(2) on day 1; cisplatin at 75 (level I) or 100 (lev el II) mg/m2 on day 1; and a continuous flourouracil infusion at 1,000 mg/m (2)/d on days 1 through 4. Patients were treated with prophylactic antibiot ics on days 5 through 15. Cycles were repeated every 21 days for a total of three cycles. Patients then received definitive therapy based on instituti onal preferences. Results: Thirteen patients were treated at level I, and 30 patients were tr eated at level II. All 43 patients were assessable for toxicity. There were no major differences in toxicity between level I and level II. Cisplatin-a ssociated grade 3 or 4 hypomagnesemia or hypocalcemia occurred in 13 (30%) and hearing lass in two patients (5%). Grade 3 or 4 neutropenia was observe d in 41 patients (95%) and febrile neutropenia occurred in eight (19%). The re was one serious infection (2%). There were 17 (40% [95% confidence inter val [CI], 25% to 56%]) clinical complete responders (CR), 23 (54% [95% CI, 39% to 69%]) partial responders (PR), one (2%) with no change, and two (5%) unassessable patients. Major responses (CR, PR) were abserved in 40 (93% [ 95% CI, 81% to 99%]) patients. Primary site CR was documented in 24 (54%) o f patients. Postchematherapy primary site biopsies were performed in 25 pat ients (58%) and pathologically negative biopsy was obtained in 11 (92%) of 12 primary site clinical CRs and seven (54%) of 13 with PR or no change. Ov erall, negative biopsies were obtained in 18 patients (72%). Conclusion: TPF induction chemotherapy can be delivered safely with a cispl atin dose of 100 mg/m2 in previously untreated patients with SCCHN. The reg imen is associated with ct high rate of primary site clinical and pathologi c CRs. Phase III comparison with cisplatinum and fluorouracil chemotherapy is warranted.