INDUCTION CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN, FLUOROURACIL, AND LEUCOVORIN FOR SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - A PHASE III TRIAL/

Purpose: A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-F U), and leucovorin (TPFL5) induction chemotherapy for patients with lo cally advanced squamous cell carcinoma of the head and neck (SCCHN). P atients and Methods: Twenty-three previously untreated patients with s tage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemother apy home support included intravenous fluids, prophytactic antibiotics , and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose wa s escalated to determine the maximum-tolerated dose (MTD). Fifteen pat ients were treated with three cycles of TPFLS at MTD. patients who ach ieved either a partial response (PR) or complete response (CR) to thre e cycles of TPFL5 then received definitive twice-daily radiation thera py. Toxicity and clinical and pathologic response to TPFL5 were assess ed. Results: Twenty-three patients received a total of 69 cycles of TP FL5. The MTD was determined to be docetaxel 60 mg/m(2). Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at M TD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium -wasting nephropathy. The overall response rate to TPFL5 was 100%, whi ch included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Fight patients had less tha n a CR in the neck to chemotherapy and, therefore, had postradiation n eck dissections, four of which were positive for residual tumor. Concl usion: TPFL5 is a tolerable induction regimen in patients with good pe rformance status. The DLT is neutropenia with significant mucositis, d iarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The hi gh response rates to TPFL5 justify further evaluation of this combinat ion of agents in the context of formal clinical trials. (C) 1998 by Am erican Society of Clinical Oncology.