Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine

Valeria Santini, Pierre Fenaux, Ghulam J. Mufti, Eva Hellström-Lindberg, Lewis R. Silverman, Alan List, Steven D. Gore, John F. Seymour, Jay Backstrom, Charles L. Beach

Research output: Contribution to journalArticle

Abstract

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 We present previously unpublished data from two large phase III trials describing common adverse events (AEs) associated with azacitidine and methods to manage them.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.

Original languageEnglish (US)
Pages (from-to)130-138
Number of pages9
JournalEuropean Journal of Haematology
Volume85
Issue number2
DOIs
StatePublished - Aug 1 2010

Keywords

  • adverse drug event
  • azacitidine
  • disease management
  • myelodysplastic syndromes
  • safety

ASJC Scopus subject areas

  • Hematology

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    Santini, V., Fenaux, P., Mufti, G. J., Hellström-Lindberg, E., Silverman, L. R., List, A., Gore, S. D., Seymour, J. F., Backstrom, J., & Beach, C. L. (2010). Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine. European Journal of Haematology, 85(2), 130-138. https://doi.org/10.1111/j.1600-0609.2010.01456.x