Phase I trial of caracemide using bolus and infusion schedules.

We conducted a phase I trial of caracemide, a new chemotherapeutic agent, which is active in the MX1 (mammary) and CX1 (colon) human tumor xenografts. Using a 5-day bolus schedule, dose-limiting toxicity consisting of burning perioral pain associated with flushing, nasal stuffiness, and excess lacrimation was seen at 650 mg/m2/day. Using a 5-day continuous-infusion schedule, dose-limiting toxicity in the form of changes in affect, lethargy, disorientation, and cognitive dysfunction with electroencephalogram abnormalities was noted at 800 mg/m2/day. The recommended phase II dose levels are 525 mg/m2/day using the 5-day bolus schedule and 650 mg/m2/day using the continuous-infusion schedule. Because of venous pain at the site of infusion, the drug must be delivered via central venous access. The pathophysiology of both the peripheral and central side effects of caracemide may be related to increased cholinergic activity.