Phase I study of MVE-2 therapy in human cancer

MVE-2, a polymer of maleic anhydride and divinyl-ether (molecular weight, 15,500), was given to 57 patients in a phase I study. The agent was selected for study because it was a potent macrophage activator, interferon inducer, and immunotherapeutic agent in animal tumor models. The drug was administered by iv infusion over a 1-hour period using three schedules of administration: (a) weekly at doses of 25-650 mg/m², (b) every other week at doses of 500-1200 mg/m², and (c) every 3 weeks at doses of 1200-1500 mg/m². No cardiac, pulmonary, hematologic, or hepatic toxicity was observed. There were 25 episodes of asymptomatic proteinuria in 26 patients who received MVE-2 dose levels of ≥ 500 mg/m². It was not associated with changes in BUN or creatinine. The proteinuria began approximately 4 weeks after the start of therapy and lasted approximately 4-6 weeks after the therapy was terminated. Proteinuria resolved in all patients followed. At present, proteinuria appears to be the major dose-limiting toxicity. None of the patients had a partial or complete response although there was evidence of biologic activity with measurable tumor regression in five patients. No major modification of host defense parameters was noted. Further studies should be directed towards determining the nature of the proteinuria and whether changes in the rate or schedule of administration can modify the proteinuria or increase the host defense modification.