A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts 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.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007372:Interferons / Q000097:blood / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011070:Poly I-C / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D007372:Interferons; D011070:Poly I-C