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

Background/Patients and methods: Thirty-two patients with recurrent head an d neck cancer (HNC) following radiotherapy and/or surgery were treated with eniluracil (10 mg/m(2)) and 5-fluorouracil (5-FU) (1 mg/m(2)) (E5F) orally twice daily for 28 days followed by a seven-day treatment free period. Thi rty-five-day cycles were repeated until disease progression, unacceptable t oxicity or patient refusal. Doses were modified for toxicity. Standard toxi city and response criteria were used. Results: Thirty-two patients were accrued; thirty-two and twenty-eight pati ents were evaluable for toxicity and response, respectively. Twelve patient s received three or more cycles of E5F. Drug related toxicities were usuall y grade 1-2 intensity and included lethargy, nausea or diarrhea (greater th an or equal to 25% of patients), and anorexia, rash or itch, stomatitis or vomiting (12%-24% of patients). Hematologic toxicity was generally mild; tw o patients experienced grade 3-5 leukopenia or thrombocytopenia. No signifi cant biochemical toxicity was seen. One patient was withdrawn (severe nause a and vomiting) and one patient died because of drug related toxicity (thro mbocytopenia). In the final analysis there were one complete and four parti al responses for a 15.6% overall response. Conclusions: E5F demonstrates activity in chemotherapy naive patients with advanced HNC cancer with acceptable toxicity profile. Further investigation of E5F with other active agents is warranted in HNC.