Phase II evaluation of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU, NSC 95466) in patients with metastatic colorectal cancer

Thirty-two patients with measurable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens received PCNU (1-(2-chloroethyl)-3-3(2,6-dioxo-3-piperidyl)-1-nitrosourea NSC 95466) on a single-day I.V. schedule administered every 6 weeks. Good-risk patients received PCNU at the starting dose of 100 mg/m², while patients who had received radiotherapy or myelosuppressive drugs such as mitomycin C received an initial dose of 75 mg/m². There were two partial remissions. Fifteen patients including four with minor tumor regression had disease stabilization. The dose-limiting toxicity was myelosuppression, with thrombocytopenia being more severe than neutropenia. The myelosuppression occurred late in the treatment cycle (days 25-32), was more severe with repeated treatments, and was more severe in patients who had a poor bone marrow reserve. Other toxicities were mild and infrequent. PCNU administered by the single-dose I.V. schedule as used in this study has very modest antitumor activity against colorectal cancer in humans.