CGP19835A, (MTP-PE) a totally synthetic muramyl tripeptide derivative related in structure to bacterial cell wall constituents, is a biologic response modifier that is believed to act by the mechanism of macrophage activation. It has shown activity against a number of murine tumor systems. Monocytes activated in vitro by MTP-PE have been shown to have in vitro activity against human tumors as well as in vitro and in vivo activity against bacterial, viral, and fungal infections. Patients are considered eligible for this study if they have evaluable or measurable cancer other than hairy cell leukemia and have failed or have no known effective conventional therapy. Patients are given a dose of MTP-PE intravenously once weekly for eight weeks. The study is an interpatient dose escalation trial with four patients at each dose. Dose levels are 0.1, 0.2, 0.4, 0.8, 1.2, 1.8, and 2.7 mg per meter squared. In addition to evaluating for toxicity and antitumor effect, patients have studies to evaluate whether the MTP-PE is activating their macrophages. Eighteen patients have been admitted to this study. The most frequent side effects have been fevers and chills occurring while or soon after the MTP-PE is infused and rapidly resolving. Mild increases or decreases in blood pressure which are transient have also been seen. There have been no chronic or serious toxicities. No antitumor responses have been seen although several patients have had stable disease, and two of these have received an additional 8 week course of treatment. Monocyte functional studies are still being evaluated. This study demonstrates that MTP-PE can be safely given by IV bolus up to at least a dose of 1.8 mg per meter squared (our current dose level) without serious toxicity. Once the maximum tolerated dose and the dose which most effectively activates monocytes have been determined, then phase II studies can be initiated to evaluate antitumor efficacy.
NIH ExPorter
NIH ExPorter