The purpose of this phase II trial was to investigate the use of paclitaxel and cisplatin in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), to evaluate tumor response, time to progression, survival, and toxicity of this regimen. Patients with recurrent and/or metastatic HNSCC received 175 mg/mq paclitaxel (PTX) administered as a 3-h intravenous infusion on day 1 and 75 mg/mq cisplatin (CDDP) as a 30(') intravenous infusion on day 2; cycles were repeated every 21 days. From February 1997 to February 2000, 36 patients (18 with locoregionally recurrent disease, 8 with deemed inoperable locally advanced disease, and 8 with metastatic disease) with a median age of 60 years (range 38-73 years) were enrolled. The patients evaluable were 34 for toxic effects, length of survival, and tumor response. The overall response was 41.1%, with two (5.8%) complete responders (CR) and 12 (35.3%) partial responders (PR), 10 (29.4%) patients had stable disease and 10 (29.4%) progressed. The median time to progression (TTP) was 5 months (range 1-49 months), and the median overall survival was 11 months (range 1-53 months). The 1-year-, the 2-year-, and the 3-year-survival rate were 38.2, 17.6 and 14.6, respectively. Up to date of the statistical evaluation four patients were still alive. According to the World Health Organization (WHO) criteria, transient G3 neutropenia and anaemia occurred in seven (20.5%) and four (11.7%) patients, respectively. The predominant non-haematologic toxicities were alopecia and fatigue: Twenty-three (67.6%) patients had G3 alopecia, two patients (5.8%) G3 fatigue and 10 (29.4%) G2, eight (23.5%) G2 myalgia, eight (23.5%) G2 nausea/vomiting, and two (5.8%) G2 mucositis. There were no G4 toxicity and any treatment-related death. Paclitaxel plus cisplatin combination is an active regimen with an acceptable safety profile in recurrent/metastatic HNSCC. This regimen, according to our opinion, is a valid alternative to infusional fluorouracil (5FU)/cisplatin. In fact up to date we can confirm, in taxane era, that paclitaxel, as single agent or in combination, produce response rates similar to cisplatin/5FU regimen, but with more manageable toxicity, especially in the subset of patients with 0-1 ECOG-PS and incurable or locoregional recurrent HNSCC, with short outpatient administration too.