PURPOSE: Flavopiridol is a cyclin-dependent kinase inhibitor that is cytotoxic to leukemic blasts. In a phase I study of flavopiridol followed by 1-beta-d-arabinofuranosylcytosine (ara-C) and mitoxantrone, overall response rate for adults with relapsed and refractory acute myelogenous leukemias (AML) was 31%. We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML. EXPERIMENTAL DESIGN: Flavopiridol (50 mg/m(2)) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 gm/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9. RESULTS: Flavopiridol caused a > or =50% decrease in peripheral blood blasts in 44% by median day 2 and > or =80% decrease in 26% by day 3. Self-limited tumor lysis occurred in 53%. Three (5%) died during therapy (2 multiorgan failure and 1 fungal pneumonia). Complete remissions (CR) were achieved in 12 of 15 (75%) newly diagnosed secondary AML, 18 of 24 (75%) first relapse after short CR (median CR, 9 months, including prior allotransplant), and 2 of 13 (15%) primary refractory but 0 of 10 multiply refractory AML. Disease-free survival for all CR patients is 40% at 2 years, with newly diagnosed patients having a 2-year disease-free survival of 50%. CONCLUSIONS: Flavopiridol has anti-AML activity directly and in combination with ara-C and mitoxantrone. This timed sequential regimen induces durable CRs in a significant proportion of adults with newly diagnosed secondary AML (including complex cytogenetics) and adults with AML in first relapse after short first CR.
PURPOSE:Flavopiridol is a cyclin-dependent kinase inhibitor that is cytotoxic to leukemic blasts. In a phase I study of flavopiridol followed by 1-beta-d-arabinofuranosylcytosine (ara-C) and mitoxantrone, overall response rate for adults with relapsed and refractory acute myelogenous leukemias (AML) was 31%. We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML. EXPERIMENTAL DESIGN:Flavopiridol (50 mg/m(2)) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 gm/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9. RESULTS:Flavopiridol caused a > or =50% decrease in peripheral blood blasts in 44% by median day 2 and > or =80% decrease in 26% by day 3. Self-limited tumor lysis occurred in 53%. Three (5%) died during therapy (2 multiorgan failure and 1 fungal pneumonia). Complete remissions (CR) were achieved in 12 of 15 (75%) newly diagnosed secondary AML, 18 of 24 (75%) first relapse after short CR (median CR, 9 months, including prior allotransplant), and 2 of 13 (15%) primary refractory but 0 of 10 multiply refractory AML. Disease-free survival for all CRpatients is 40% at 2 years, with newly diagnosed patients having a 2-year disease-free survival of 50%. CONCLUSIONS:Flavopiridol has anti-AML activity directly and in combination with ara-C and mitoxantrone. This timed sequential regimen induces durable CRs in a significant proportion of adults with newly diagnosed secondary AML (including complex cytogenetics) and adults with AML in first relapse after short first CR.
Authors: David M Lucas; Patrick C Still; Lynette Bueno Pérez; Michael R Grever; A Douglas Kinghorn Journal: Curr Drug Targets Date: 2010-07 Impact factor: 3.465
Authors: Elizabeth A Griffiths; Steven D Gore; Craig M Hooker; Helai P Mohammad; Michael A McDevitt; B Douglas Smith; Judith E Karp; James G Herman; Hetty E Carraway Journal: Epigenetics Date: 2010-10-01 Impact factor: 4.528
Authors: N Nitta; A Sonoda; A Seko; S Ohta; Y Nagatani; K Tsuchiya; H Otani; T Tanaka; S Kanasaki; M Takahashi; K Murata Journal: Br J Radiol Date: 2009-12-17 Impact factor: 3.039
Authors: Judith E Karp; Amanda Blackford; B Douglas Smith; Katrina Alino; Amy Hatfield Seung; Javier Bolaños-Meade; Jacqueline M Greer; Hetty E Carraway; Steven D Gore; Richard J Jones; Mark J Levis; Michael A McDevitt; L Austin Doyle; John J Wright Journal: Leuk Res Date: 2009-12-04 Impact factor: 3.156