Systemic administration of a phosphorothioate oligonucleotide with a sequence complementary to p53 for acute myelogenous leukemia and myelodysplastic …
E Bayever, PL Iversen, MR Bishop… - Antisense research …, 1993 - liebertpub.com
E Bayever, PL Iversen, MR Bishop, JG Sharp, HK Tewary, MA Arneson, SJ Pirruccello…
Antisense research and development, 1993•liebertpub.comA synthetic phosphorothioate oligonucleotide was administered systemically to five patients
with either relapsed or refractory acute myelogenous leukemia (AML), or myelodysplastic
syndrome (MDS). Patients received a 10-day continuous intravenous infusion of this
compound, which is complementary to p53 mRNA. No major toxicity attributable to a dose of
0.05 mg/kg/hr was observed. A range of approximately 9 to 18% of the administered dose
was recovered in the urine as intact oligonucleotide. Evaluation of malignant cells recovered …
with either relapsed or refractory acute myelogenous leukemia (AML), or myelodysplastic
syndrome (MDS). Patients received a 10-day continuous intravenous infusion of this
compound, which is complementary to p53 mRNA. No major toxicity attributable to a dose of
0.05 mg/kg/hr was observed. A range of approximately 9 to 18% of the administered dose
was recovered in the urine as intact oligonucleotide. Evaluation of malignant cells recovered …
A synthetic phosphorothioate oligonucleotide was administered systemically to five patients with either relapsed or refractory acute myelogenous leukemia (AML), or myelodysplastic syndrome (MDS). Patients received a 10-day continuous intravenous infusion of this compound, which is complementary to p53 mRNA. No major toxicity attributable to a dose of 0.05 mg/kg/hr was observed. A range of approximately 9 to 18% of the administered dose was recovered in the urine as intact oligonucleotide. Evaluation of malignant cells recovered from bone marrow and peripheral blood at intervals before, during, and after treatment reveals no enhanced growth potential following oligonucleotide administration. Hence, a phosphorothioate oligonucleotide complementary to p53 mRNA can be administered at this dose level to humans without major toxicity. Higher doses need to be evaluated for toxicity and potential clinical efficacy.
Mary Ann Liebert