Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*.
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 We present previously unpublished data from two large phase III trials describing common adverse events (AEs) associated with azacitidine and methods to manage them.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.


CONCLUSIONS
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.
Santini
Valeria
V
Azienda Ospedaliera Universitaria Careggi, Florence, Italy. valeria.santini@unifi.it
Fenaux
Pierre
P
Mufti
Ghulam J
GJ
Hellström-Lindberg
Eva
E
Silverman
Lewis R
LR
List
Alan
A
Gore
Steven D
SD
Seymour
John F
JF
Backstrom
Jay
J
Beach
Charles L
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory; D000754:Anemia, Refractory, with Excess of Blasts; D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine / Q000009:adverse effects*; D019468:Disease Management; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
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