BACKGROUND:Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m(2) vs 30 mg/m(2) daily × 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m(2) and 29% at 30 mg/m(2)). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m(2) of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.
RCT Entities:
BACKGROUND:Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m(2) vs 30 mg/m(2) daily × 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m(2) and 29% at 30 mg/m(2)). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m(2) of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.
Authors: P Greenberg; C Cox; M M LeBeau; P Fenaux; P Morel; G Sanz; M Sanz; T Vallespi; T Hamblin; D Oscier; K Ohyashiki; K Toyama; C Aul; G Mufti; J Bennett Journal: Blood Date: 1997-03-15 Impact factor: 22.113
Authors: Bruce D Cheson; Peter L Greenberg; John M Bennett; Bob Lowenberg; Pierre W Wijermans; Stephen D Nimer; Antonio Pinto; Miloslav Beran; Theo M de Witte; Richard M Stone; Moshe Mittelman; Guillermo F Sanz; Steven D Gore; Charles A Schiffer; Hagop Kantarjian Journal: Blood Date: 2006-04-11 Impact factor: 22.113
Authors: Lewis R Silverman; Erin P Demakos; Bercedis L Peterson; Alice B Kornblith; Jimmie C Holland; Rosalie Odchimar-Reissig; Richard M Stone; Douglas Nelson; Bayard L Powell; Carlos M DeCastro; John Ellerton; Richard A Larson; Charles A Schiffer; James F Holland Journal: J Clin Oncol Date: 2002-05-15 Impact factor: 44.544
Authors: Stefan Faderl; Varsha Gandhi; Susan O'Brien; Peter Bonate; Jorge Cortes; Elihu Estey; Miloslav Beran; William Wierda; Guillermo Garcia-Manero; Alessandra Ferrajoli; Zeev Estrov; Francis J Giles; Min Du; Monica Kwari; Michael Keating; William Plunkett; Hagop Kantarjian Journal: Blood Date: 2004-10-14 Impact factor: 22.113
Authors: Hagop Kantarjian; Jean-Pierre J Issa; Craig S Rosenfeld; John M Bennett; Maher Albitar; John DiPersio; Virginia Klimek; James Slack; Carlos de Castro; Farhad Ravandi; Richard Helmer; Lanlan Shen; Stephen D Nimer; Richard Leavitt; Azra Raza; Hussain Saba Journal: Cancer Date: 2006-04-15 Impact factor: 6.860
Authors: Hagop M Kantarjian; Varsha Gandhi; Peter Kozuch; Stefan Faderl; Francis Giles; Jorge Cortes; Susan O'Brien; Nuhad Ibrahim; Fadlo Khuri; Min Du; Mary Beth Rios; Sima Jeha; Peter McLaughlin; William Plunkett; Michael Keating Journal: J Clin Oncol Date: 2003-03-15 Impact factor: 44.544
Authors: Hagop Kantarjian; Varsha Gandhi; Jorge Cortes; Srdan Verstovsek; Min Du; Guillermo Garcia-Manero; Francis Giles; Stefan Faderl; Susan O'Brien; Sima Jeha; Jan Davis; Zeev Shaked; Adam Craig; Michael Keating; William Plunkett; Emil J Freireich Journal: Blood Date: 2003-06-05 Impact factor: 22.113
Authors: Camille R Petri; Peter H O'Donnell; Hongyuan Cao; Andrew S Artz; Wendy Stock; Amittha Wickrema; Marjie Hard; Koen van Besien Journal: Leuk Lymphoma Date: 2014-05-27