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

The combination of cisplatin and 5-fluorouracil (5-FU) is considered standard therapy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Paclitaxel has exhibited single-agent activity in patients with this disease. The authors conducted this study to evaluate the feasibility and efficacy of combining paclitaxel with cisplatin and 5-FU for patients with advanced or recurrent SCCHN. Patients with recurrent, metastatic, or locally advanced SCCHN who had measurable or evaluable disease and no prior chemotherapy were eligible. The starting dose level consisted of paclitaxel 135 mg/m(2) on Day 1, cisplatin 75 mg/m(2) on Day 2, and 5-FU 1 gm/m(2)/day on Days 2-6. Due to Grade 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). Twenty-five patients were enrolled, with a median age of 60 years and a median Southwest Oncology Group performance status of 1. Of the 25 patients, 16 had recurrent disease, 3 had metastatic disease at diagnosis, and 6 had untreated locally advanced SCCHN. Ninety-nine courses of therapy were administered, with a median of 5 courses. Major toxicities were neutropenia and mucositis. Significant neurotoxicity or nephrotoxicity were not observed. There were two treatment-related deaths (one each due to mucositis and neutropenic pneumonia), and these precluded further dose escalation. Fifteen 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 metastatic 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+ months' duration, respectively. The median survival for patients with recurrent or metastatic disease was 6 months (range, 1-26 months), with a 1-year survival rate of 37%. The dose and schedule for the combination of paclitaxel, 5-FU, and cisplatin as determined in this study are feasible, with encouraging outcomes and activity in patients with recurrent or metastatic SCCHN. The results of this trial warrant larger-scale evaluation to determine the role of this combination in the management of patients with this disease.

Hussain M ，Gadgeel S ，Kucuk O ，Du W ，Salwen W ，Ensley J ... -  《CANCER》

Paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: a preliminary report.

Hussain M ，Salwen W ，Kucuk O ，Ensley J ... -  《SEMINARS IN ONCOLOGY》

A phase II evaluation of a 3-hour infusion of paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: Southwest Oncology Group study 0007.

Worden FP ，Moon J ，Samlowski W ，Clark JI ，Dakhil SR ，Williamson S ，Urba SG ，Ensley J ，Hussain MH ，Southwest Oncology Group, Head and Neck Working Group ... -  《CANCER》

Role of paclitaxel, ifosfamide, and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Shin DM ，Glisson BS ，Khuri FR ，Hong WK ，Lippman SM ... -  《SEMINARS IN ONCOLOGY》

Phase II trial of dose-dense paclitaxel, cisplatin, 5-fluorouracil, and leucovorin with filgrastim support in patients with squamous cell carcinoma of the head and neck.

The current study evaluated the feasibility and clinical activity of a combination of paclitaxel, cisplatin, 5-fluorouracil (5-FU), and leucovorin administered on a biweekly schedule to patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC). Patients with recurrent or unresectable HNSCC were eligible if they had received a previous regimen of neoadjuvant chemotherapy, concurrent chemoradiotherapy, or no previous systemic therapy. Patients received paclitaxel (175 mg/m2 on Day 1), cisplatin (35 mg/m2 on Days 1 and 2), leucovorin (200 mg/m2 on Day 1), and 5-FU (1000 mg/m2 per day as a 48-hour continuous intravenous infusion on Days 1 and 2) every 2 weeks. Patients received subcutaneous filgrastim (300 microg per day) on Days 3-9 of each cycle. Treatment was administered on an outpatient basis for a maximum of six cycles. Thirty-five patients received a combined total of 194 treatment cycles. Eighteen complete responses (51%) and 12 partial responses (34%) were documented, for an overall response rate of 86% (30 of 35 patients). The median progression-free survival duration was 14 months, and the median overall survival duration was 18 months. Two toxicity-related deaths were documented (one due to neutropenic sepsis and the other due to catheter-related pulmonary embolism). Grade 4 neutropenia was observed in one patient. Other severe (Grade 3 or 4) toxic effects included mucositis (14%), anemia (6%), thrombosis (6%), thrombocytopenia (3%), and neuropathy (3%). The current dose-dense, four-agent, taxane-containing biweekly schedule was feasible and effective in patients with recurrent or unresectable HNSCC. However, given the single-center nature of the current study and the highly selected study population, further validation of these findings is recommended.

Hitt R ，Jimeno A ，Millán JM ，Castellano D ，Cortés-Funes H ... -  《CANCER》