Sulofenur is a member of a new class of antineoplastic agents with a novel chemical structure and unique pharmacological and biological properties. Preclinical studies have demonstrated a wide spectrum of anti-tumor activity against murine solid tumors and human tumor xenografts. In phase I trials, only mild toxicities were observed. Twenty-six patients (pts), two of whom were inevaluable, with advanced non small cell lung cancer without prior chemotherapy were entered on this phase II trial. Pts received 800 mg/m2 sulofenur po Monday-Friday x 21 days, q 28 days. Seventeen male and 9 female pts with median performance status 1 received a median of 2 courses. Twenty pts had stage IV disease and 19 pts had adenocarcinoma, 6 squamous cell and 1 undifferentiated carcinoma. The main toxicity was grade 1 to 3 anemia in 16 (62%) pts, with hemolysis noted in 9 pts. Although methemoglobinemia was observed in 19 pts, it was severe in only 3 pts. Transient elevation of alkaline phosphatase was seen in 11 pts and one pt had a minor abnormality in glucose metabolism. Other common chemotherapy related side effects such as granulocytopenia or alopecia were not encountered with this agent. Of 24 evaluable pts, two pts had stable disease or minor response and 22 pts had progressive disease. In conclusion although sulofenur had only minor side effects, in the dosage and schedule used, it did not produce any significant response in advanced non-small cell lung cancer.