PHASE-I STUDY OF VRCTC-310, A PURIFIED PHOSPHOLIPASE A(2) PURIFIED FROM SNAKE-VENOM, IN PATIENTS WITH REFRACTORY CANCER - SAFETY AND PHARMACOKINETIC DATA

A phase I study was performed to evaluate the maximum tolerated dose ( MTD), safety profile and pharmacokinetic data with VRCTC-310, a natura l product derived from purified snake venom fractions, with phospholip ase A(2) activity and inhibitory effects against human and murine tumo r cell lines. Fifteen patients with refractory malignancies were enter ed after providing written informed consent. VRCTC-310 was administere d as an intramuscular injection daily for 30 consecutive days. Doses w ere escalated from 0.0025 to 0.023 mg/kg. Toxicities included local pa in at the injection site, eosinophilia, reversible diplopia and palpeb ral ptosis. Dose escalation was stopped at 0.023 mg/kg, when two patie nts had developed anaphylactoid reactions. Both cases had high VRCTC-3 10-specific IgG by EIA. MTD was 0.017 mg/kg and the recommended dose f or phase II studies is 0.017 mg/kg. Stabilization was found in six pat ients.