Systemic Administration of a Phosphorothioate Oligonucleotide with a Sequence Complementary to p53 for Acute Myelogenous Leukemia and Myelodysplastic Syndrome: Initial Results of a Phase I Trial

摘要: A synthetic phosphorothioate oligonucleotide was administered systemically to five patients with either relapsed or refractory acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS). Patients received a 10-day continuous intravenous infusion of this compound, which is complementary p53 mRNA. No major toxicity attributable dose 0.05 mg/kg/hr observed. range approximately 9 18% the recovered in urine as intact oligonucleotide. Evaluation malignant cells from bone marrow and peripheral blood at intervals before, during, after treatment reveals no enhanced growth potential following administration. Hence, mRNA can be level humans without toxicity. Higher doses need evaluated for clinical efficacy.