A phase I-II trial of multiple-dose polyriboinosinic-polyribocytidylic acid in patients with leukemia or solid tumors

Abstract

Polyriboinosinic-polyribocytidylic acid (poly I · poly C), an interferon inducer, was administered in multiple doses of 0.3-75 mg/m2 to 26 patients with a variety of solid tumors, 9 with acute leukemia, and 2 with chronic myelogenous leukemia in blast crisis. Forty-four separate drug trials were comprised of various schedules and routes of administration. Toxic reactions included fever (in 66% of the trials), transient elevation of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase (25%), minimal laboratory evidence of coagulation abnormalities (59%), and hypersensitivity (5%). These toxic manifestations did not relate to dose level or magnitude of interferon induction. poly I · poly C administered iv induced low serum concentrations of interferon in 24/38 trials (63%), but the correlation between drug dose and peak interferon titer was not linear. poly I · poly C administered iv or im was not effective as an inducer of interferon in the cerebrospinal fluid. Similarly, poly I · poly C administered im or by inhalation did not produce detectable serum levels of interferon. No patients experienced an objective tumor response to the administration of poly I · poly C, and most (76%) had progression of their disease while receiving the drug. © 1976, Oxford University Press. All rights reserved.