Paclitaxel, cisplatin, and 5-fluorouracil for patients with advanced or recurrent squamous cell carcinoma of the head and neck

BACKGROUND, The combination of cisplatin and 5-flurouracil (5-FU] is consid ered standard therapy for patients with recurrent or metastatic squamous ce ll carcinoma of the head and neck (SCCHN). Paclitaxel has exhibited single- agent activity in patients with this disease. The authors conducted this st udy to evaluate the feasibility and efficacy of combining paclitaxel with c isplatin and 5-FU for patients with advanced or recurrent SCCHN. METHODS, Patients with recurrent, metastatic, or locally advanced SCCHN who had measurable or evaluable disease and no prior chemotherapy were eligibl e. The starting dose level consisted of paclitaxel 135 mg/m(2) on Day 1, ci splatin 75 mg/m(2) on Day 2, and 5-FU 1 gm/m(2)/day on Days 2-6. Due to Gra de 4 mucositis, dose level 1 of 5-FU was reduced to 800 mg/m(2)/day on Days 2-6 (for 7 patients), and subsequently the 5-FU dose was adjusted to 1 gm/ m(2)/day on Days 2-5 (for 17 patients). RESULTS. Twenty-five patients were enrolled,with a median age of 60 years a nd a median Southwest Oncology Group performance status of 1. Of the 25 pat ients, 16 had recurrent disease, 3 had metastatic disease at diagnosis, and 6 had untreated locally advanced SCCHN. Ninety-nine courses of therapy wer e administered, with a median of 5 courses. Major toxicities were neutropen ia and mucositis. Significant neurotoxicity or nephrotoxicity were not obse rved. There were two treatment related deaths tone each due to mucositis an d neutropenic pneumonia), and these precluded further dose escalation. Fift een of the 25 patients (60%) achieved a major response. Of significance is the response rate of 58% (11 of 19 patients) in those with recurrent or met astatic disease who had a duration of response ranging from 3 to 19+ months . Two of these 19 patients continue to be in remission of 19+ and 15+ month s' duration, respectively. The median survival for patients with recurrent or metastatic disease was 6 months (range, 1-26 months), with a 1-year surv ival rate of 37%. CONCLUSIONS, The dose and schedule for the combination of paclitaxel, 5-FU, and cisplatin as determined in this study are feasible, with encouraging o utcomes and activity in patients with recurrent or metastatic SCCHN. The re sults of this trial warrant larger-scale evaluation to determine the role o f this combination in the management of patients with this disease. (C) 199 9 American Cancer Society.