Faculty Collaboration Database

Phase I/IB study of polyadenylic-polyuridylic acid in patients with advanced malignancies: clinical and biologic effects. J Interferon Cytokine Res 1996 Aug;16(8):631-5

Date

08/01/1996

Pubmed ID

8877734

DOI

10.1089/jir.1996.16.631

Scopus ID

2-s2.0-0029844046 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

The synthetic polynucleotide polyadenylic-polyuridylic acid (polyA:polyU) has shown antitumor activity in murine studies and human breast cancer. PolyA:polyU was evaluated in 25 cancer patients receiving weekly intravenous doses between 3 and 600 mg/m2. PolyA:polyU was well tolerated up to 600 mg/m2, with no doselimiting toxicity (all < grade 3). Side effects included mild elevation in temperature, fatigue, and mild hyperglycemia. No changes outside of the normal range in hematocrit, WBC count, platelet count, total bilirubin, or alkaline phosphatase were observed. Of 25 patients, 18 completed at least one cycle of 6 weeks, and 5 completed two cycles (median 6 weeks). Four patients had stable disease over 11-13 weeks of treatment, and no clinical responses were observed. At 24 h after the first treatment, there were no significant increases in biologic response (beta 2-microglobulin and neopterin in serum, or 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells). A small increase in beta 2-microglobulin was observed 24 h after the week 3 treatment (1.1-fold, p < 0.01). By the third week of treatment, 2-5A synthetase levels decreased slightly (to 80% of baseline, p < 0.01). No changes in cytokines IL-6, IL-12, tumor necrosis factor (TNF), or IL-2 receptor in serum were detected after 24 h of treatment. Thus, at these doses, polyA:polyU had no marked modulation on biologic responses in vivo, although this preparation significantly induced 2-5A synthetase in peripheral blood mononuclear cells in vitro. PolyA:polyU was well tolerated. An MTD was not reached but was greater than 600 mg/m2 on this weekly schedule.

Author List

Witt PL, Zahir S, Ritch PS, McAuliffe TM, Ewel CH, Borden EC

Author

Timothy L. McAuliffe PhD Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

2',5'-Oligoadenylate Synthetase
Adult
Aged
Antineoplastic Agents
Cytokines
Fatigue
Female
Fever
Humans
Hyperglycemia
Interferon Inducers
Male
Middle Aged
Neoplasm Proteins
Neoplasms
Neopterin
Poly A-U
Treatment Outcome
beta 2-Microglobulin