CI-980 (NSC 370147)--a synthetic mitotic inhibitor that binds to
tubulin at the
colchicine binding site--has significant activity against a broad spectrum of
tumor models and greater in vitro cytotoxicity when given over > 24 hours than 4 hours or less. Phase I studies demonstrated central nervous system (CNS) toxicity to be dose-limiting when
CI-980 was administered as a 24-hour infusion. When a 72-hour infusion was given, CNS toxicity was reduced and
granulocytopenia became the dose-limiting toxicity. In this phase II study,
CI-980, 4.5 mg/m2, was administered as a 24-hour continuous
intravenous infusion for 3 consecutive days and repeated every 21 days. Fourteen patients who had measurable metastatic
colorectal cancer were entered in the trial. Eight patients had received one prior
chemotherapy regimen for metastatic disease. Patients were prospectively monitored by neurologic examinations and neuropsychologic assessment of cognitive functioning. No complete or partial responses were observed. Grade 4
granulocytopenia was the dose-limiting toxicity. Reversible declines in recent memory function were noted in all patients. After each course of
CI-980, there were also transient non-significant declines in motor coordination, compared with the preinfusion assessment. At the stated dose and schedule,
CI-980 lacks activity in metastatic
colorectal carcinoma. The agent's toxicity profile (
granulocytopenia and CNS effects) was comparable with previously described effects of this agent.