38 research outputs found
Prospective randomized feasibility trial to assess the use of rhPDGF-BB in treatment of distal radius fractures
Renal transplantation for end-stage renal disease due to paroxysmal nocturnal haemoglobinuria
Ulnar Shortening for the Treatment of Early Post-Traumatic Osteoarthritis at the Distal Radioulnar Joint
Lipid Peroxidation and Antioxidant Activity in Chronic Haemodialysis Patients Treated with Recombinant Human Erythropoietin
Salvage of Failed SauvĂ©âKapandji Procedure with an Ulnar Head Prosthesis: Report of Three Cases
Frayed Ulno-Triquetral and Ulno-Lunate Ligaments as an Arthroscopic Sign of Longstanding Triquetro-Lunate Ligament Rupture
A phase I first-in-human study with tefinostat - a monocyte/macrophage targeted histone deacetylase inhibitor - in patients with advanced haematological malignancies
Phase I/II Clinical Study of Tosedostat, an Inhibitor of Aminopeptidases, in Patients With Acute Myeloid Leukemia and Myelodysplasia
Purpose. To identify the maximum-tolerated dose (MTD) and to evaluate the antileukemic activity of tosedostat (formerly CHR-2797), an orally bioavailable aminopeptidase inhibitor.
Patients and Methods. In phase I, the MTD of once daily oral doses of tosedostat in hematologic malignancies was defined. In phase II, the therapeutic activity of the maximum-acceptable dose (MAD) of tosedostat was evaluated in elderly and/or relapsing patients with acute myeloid leukemia (AML) or myelodysplastic syndrome.
Results. In phase I, 16 patients were treated in four cohorts with tosedostat (60 mg to 180 mg) for 28 days. Three patients reported dose-limiting toxicities: two with reversible thrombocytopenia (> 75% reduction in platelet count) at 180 mg (MTD) and one with a Common Toxicity Criteria (CTC) grade 3 ALT elevation at 130 mg (MAD). In phase II, 41 patients were treated with 130 mg tosedostat. In phases I and II, the most common severe (CTC grades 3 to 5) adverse event was a reduction in the platelet count. Of the 51 AML patients in this study, seven reached complete marrow response ( 60 years, and 79% had either relapsed or refractory AML.
Conclusion. This phase I/II study demonstrates that oral once daily dosing with 130 mg tosedostat is well tolerated and has significant antileukemic activity. The favorable risk-benefit profile suggests that further clinical trials are warranted