OBJECTIVE: Myelodysplastic syndrome (MDS) treatment can initially worsen patients' clinical condition and they may discontinue therapy before achieving benefit. We present previously unpublished data from two large phase III trials describing common adverse events (AEs) associated with azacitidine and methods to manage them. METHODS: In the Cancer and Leukemia Group B (CALGB) 9221 study, patients with any French-American-British (FAB) subtype of MDS were randomized to azacitidine or best supportive care (BSC). After 56 d, patients randomized to BSC with disease progression could cross over to receive azacitidine. In the AZA-001 study, patients with higher-risk MDS (FAB-defined refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocitic leukaemia and IPSS int-2 or high) were randomized to azacitidine or to conventional care regimens (CCR), which included low-dose ara-C, BSC, or intensive chemotherapy. In both studies, azacitidine dose was 75 mg/m(2)/d SC for 7 d every 28 d. AEs were graded per National Cancer Institute's Common Toxicity Criteria version 2.0 (AZA-001) or CALGB Expanded CTC (CALGB 9221). RESULTS: In safety-evaluable patients in AZA-001 (N = 175) or CALGB 9221 (N = 150), the most common AEs with azacitidine included hematologic (eg, cytopenias) and non-hematologic administration-related events (eg, injection-site reactions and gastrointestinal disorders). Most AEs were transient and resolved during ongoing therapy (> 83%). Hematologic AEs, most frequently observed during early treatment cycles, decreased during subsequent cycles and were usually managed with dosing delays (23-29%). Gastrointestinal symptoms were primarily managed with anti-emetics and laxatives. CONCLUSION: Hematologic and non-hematologic AEs with azacitidine decreased in frequency as treatment continued. Awareness of the onset, duration and management of AEs can facilitate treatment, permitting patients to continue therapy for maximum benefit.
RCT Entities:
OBJECTIVE:Myelodysplastic syndrome (MDS) treatment can initially worsen patients' clinical condition and they may discontinue therapy before achieving benefit. We present previously unpublished data from two large phase III trials describing common adverse events (AEs) associated with azacitidine and methods to manage them. METHODS: In the Cancer and Leukemia Group B (CALGB) 9221 study, patients with any French-American-British (FAB) subtype of MDS were randomized to azacitidine or best supportive care (BSC). After 56 d, patients randomized to BSC with disease progression could cross over to receive azacitidine. In the AZA-001 study, patients with higher-risk MDS (FAB-defined refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocitic leukaemia and IPSS int-2 or high) were randomized to azacitidine or to conventional care regimens (CCR), which included low-dose ara-C, BSC, or intensive chemotherapy. In both studies, azacitidine dose was 75 mg/m(2)/d SC for 7 d every 28 d. AEs were graded per National Cancer Institute's Common Toxicity Criteria version 2.0 (AZA-001) or CALGB Expanded CTC (CALGB 9221). RESULTS: In safety-evaluable patients in AZA-001 (N = 175) or CALGB 9221 (N = 150), the most common AEs with azacitidine included hematologic (eg, cytopenias) and non-hematologic administration-related events (eg, injection-site reactions and gastrointestinal disorders). Most AEs were transient and resolved during ongoing therapy (> 83%). Hematologic AEs, most frequently observed during early treatment cycles, decreased during subsequent cycles and were usually managed with dosing delays (23-29%). Gastrointestinal symptoms were primarily managed with anti-emetics and laxatives. CONCLUSION: Hematologic and non-hematologic AEs with azacitidine decreased in frequency as treatment continued. Awareness of the onset, duration and management of AEs can facilitate treatment, permitting patients to continue therapy for maximum benefit.
Authors: David Bowen; Dominic Culligan; Simon Jowitt; Stephen Kelsey; Ghulam Mufti; David Oscier; Jane Parker Journal: Br J Haematol Date: 2003-01 Impact factor: 6.998
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: Lewis R Silverman; David R McKenzie; Bercedis L Peterson; James F Holland; Jay T Backstrom; C L Beach; Richard A Larson Journal: J Clin Oncol Date: 2006-08-20 Impact factor: 44.544
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: Alice B Kornblith; James E Herndon; Lewis R Silverman; Erin P Demakos; Rosalie Odchimar-Reissig; James F Holland; Bayard L Powell; Carlos DeCastro; John Ellerton; Richard A Larson; Charles A Schiffer; Jimmie C Holland Journal: J Clin Oncol Date: 2002-05-15 Impact factor: 44.544
Authors: Pierre Fenaux; Ghulam J Mufti; Eva Hellstrom-Lindberg; Valeria Santini; Carlo Finelli; Aristoteles Giagounidis; Robert Schoch; Norbert Gattermann; Guillermo Sanz; Alan List; Steven D Gore; John F Seymour; John M Bennett; John Byrd; Jay Backstrom; Linda Zimmerman; David McKenzie; Cl Beach; Lewis R Silverman Journal: Lancet Oncol Date: 2009-02-21 Impact factor: 41.316
Authors: Mikkael A Sekeres; W Marieke Schoonen; Hagop Kantarjian; Alan List; Jon Fryzek; Ronald Paquette; Jaroslaw P Maciejewski Journal: J Natl Cancer Inst Date: 2008-10-28 Impact factor: 13.506
Authors: Emilio Paolo Alessandrino; Sergio Amadori; Giovanni Barosi; Mario Cazzola; Alberto Grossi; Lucio N Liberato; Franco Locatelli; Monia Marchetti; Enrica Morra; Paolo Rebulla; Giuseppe Visani; Sante Tura Journal: Haematologica Date: 2002-12 Impact factor: 9.941
Authors: Roger M Lyons; Thomas M Cosgriff; Sanjiv S Modi; Robert H Gersh; John D Hainsworth; Allen L Cohn; Heidi J McIntyre; Indra J Fernando; Jay T Backstrom; C L Beach Journal: J Clin Oncol Date: 2009-03-02 Impact factor: 44.544
Authors: John F Seymour; Pierre Fenaux; Lewis R Silverman; Ghulam J Mufti; Eva Hellström-Lindberg; Valeria Santini; Alan F List; Steven D Gore; Jay Backstrom; David McKenzie; C L Beach Journal: Crit Rev Oncol Hematol Date: 2010-05-06 Impact factor: 6.312