A National Cancer Institute of Canada Clinical Trials Group phase II study of eniluracil (776C85) and oral 5-fluorouracil in patients with advanced squamous cell head and neck cancer

Background/Patients and methods:Thirty-two patients withrecurrent head and neck cancer (HNC) following radiotherapy and/or surgerywere treated with eniluracil (10 mg/m²) and 5-fluorouracil (5-FU)(1 mg/m²) (E5F) orally twice daily for 28 days followed by aseven-day treatment free period. Thirty-five-day cycles were repeated untildisease progression, unacceptable toxicity or patient refusal. Doses weremodified for toxicity. Standard toxicity and response criteria were used.Results:Thirty-two patients were accrued; thirty-two andtwenty-eight patients were evaluable for toxicity and response, respectively.Twelve patients received three or more cycles of E5F. Drug related toxicitieswere usually grade 1–2 intensity and included lethargy, nausea ordiarrhea (25% of patients), and anorexia, rash or itch, stomatitisor vomiting (12%–24% of patients). Hematologic toxicitywas generally mild; two patients experienced grade 3–5 leukopenia orthrombocytopenia. No significant biochemical toxicity was seen. One patientwas withdrawn (severe nausea and vomiting) and one patient died because ofdrug related toxicity (thrombocytopenia). In the final analysis there were onecomplete and four partial responses for a 15.6% overall response.Conclusions:E5F demonstrates activity in chemotherapy naïvepatients with advanced HNC cancer with acceptable toxicity profile. Furtherinvestigation of E5F with other active agents is warranted in HNC.