Phase II clinical evaluation of AZQ in colorectal cancer

Thirty patients with measurable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens, received AZQ (1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)3,5,dioxo,diethylester, NSC 182986) on a 5-day intravenous schedule administered every 4 weeks. Good risk patients received AZQ at the starting daily dose of 8 mg/m², while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 6 mg/m². There were no complete or partial remissions. Only one of 27 evaluable patients had objective tumor regression. Five additional patients had disease stabilization. The dose-limiting toxicity was myelosuppression, with thrombocytopenia being more severe than neutropenia. The myelosuppression occurred late in the treatment cycle (day 20), was more severe with repeated treatments, and was more severe in patients who had poor bone marrow reserves. AZQ administered by the 5-day dose schedule as used in this study is not effective against colorectal cancer.