Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies.

• DOI: 10.1200/jco.1996.14.4.1320
• Publication Date: 2017-02-24T09:46:12Z
• Authors: M R Bishop; P L Iversen; E Bayever; J G Sharp; T C Greiner; B L Copple; R Ruddon; G Zon; J Spinolo; M Arneson; J O Armitage; A Kessinger
• Keywords: Refractory (planetary science)

PURPOSE The phosphoprotein p53 is involved in transcriptional regulation and detected hematologic malignancies. In vitro incubation of acute myelogenous leukemia with OL(1)p53, a 20-mer phosphorothioate oligonucleotide complementary to mRNA, results leukemic cell death. A phase I dose-escalating trial was conducted determine the toxicity OL(1)p53 following systemic administration patients PATIENTS AND METHODS Sixteen either refractory (n = 6) or advanced myelodysplastic syndrome 10) participated trial. Patients were given at doses 0.05 0.25 mg/kg/h for 10 days by continuous intravenous infusion. RESULTS No specific directly related OL(1)p53. One patient developed transient nonoliguric renal failure. died anthracycline-induced cardiac Approximately 36% administered dose recovered intact urine. Plasma concentrations area under plasma concentration curves linearly correlated dose. Leukemic growth inhibited as compared pretreatment samples. There no clinical complete responses. CONCLUSION oligonucleotide, can be systemically without complications. This type modified degradation, it from urine intact. may useful combination currently available chemotherapy agents treatment