A phase I clinical tolerance study of polyadenylic-polyuridylic acid in cancer patients.

Polyadenylic-polyuridylic acid [poly(A) X poly(U)], an immunomodulator, has been shown to have antitumor effects in rodents and in a randomized clinical trial as an adjuvant to surgery in patients with operable breast cancer. The purpose of the present study was to determine the following: (a) clinical tolerance and safety of poly(A) X poly(U) in 13 patients with advanced cancer receiving a single dose of this duplex, using increasing amounts per intravenous injection of 90, 180, 300, and 450 mg; (b) if such high doses increased the level of interferon-mediated protein kinase and enhanced natural killer (NK) cell activity as observed previously with lower doses; and (c) if circulating interferon could be detected. No toxicity was observed in the 13 patients by close observation of clinical parameters, hemogram, and renal and liver functions. Increases of interferon-mediated protein kinase and of NK cell activity were observed, but there was no correlation between the magnitude of the responses and the dose of poly(A) X poly(U). No circulating interferon was detected. We conclude that poly(A) X poly(U) is not toxic in humans, at least up to a dose of 450 mg.