A Phase I–II Trial of Multiple-Dose Polyriboinosinic-Polyribocytidylic Acid in Patients With Leukemia or Solid Tumors

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.