A phase II study of piritrexim in patients with advanced squamous head and neck cancer

Piritrexim (PTX) is a newly developed lipid‐soluble folate antagonist that crosses the cell membrane by a simple, rapid, carrier‐independent diffusion process. A Phase II study was conducted to evaluate the activity of PTX in 34 patients with previously chemotherapy‐naive squamous cell cancer of the head and neck area (SCCHN). Among them, 30 patients had received previous radiation therapy and/or surgery. Of 33 patients who could be examined, 3 had a complete response (CR), 6 had a partial response (PR), 11 had no change, and 13 had disease progression. The overall response rate (CR + PR) was 27% (9 of 33; 95% confidence interval, 13% to 46%). The response duration ranged from 36 to 360+ days (median, 162) and was similar to the best studies reported with methotrexate. The three most severe side effects (Grades 3 and 4 by World Health Organization criteria) were leukopenia, thrombocytopenia, and mucositis. These occurred in 41%, 26%, and 15% of the 34 patients, respectively. This study established PTX as an agent with some activity in SCCHN. The use of PTX in combination chemotherapeutic regimens needs to be explored. Cancer 1992; 69:1008–1011.