Feasibility of therapy with hypomethylating agents in patients with renal insufficiency.
BACKGROUND
To our knowledge, the feasibility of therapy with hypomethylating agents (HAs) in patients with renal insufficiency (RI) has not been examined.


METHODS
We reviewed 41 patients with a diagnosis of acute myeloid leukemia (n = 17), myelodysplastic syndromes (n = 15), and chronic myelomonocytic leukemia (n = 9) who had RI and were receiving therapy with azacitidine or decitabine. The median number of administered cycles was 3. Most patients (39; 95%) received a standard dose of the drugs at the initiation of therapy. Nine patients (22%) required treatment interruptions or discontinuation, and 10 patients (24%) required dose reductions.


RESULTS
The overall response rate was 63%, and 4 patients (10%) achieved a complete response. Twenty patients (51%) experienced grade 3 or 4 myelosuppression-related toxicities. Hospitalization was required in 68% of the patients. Among 12 patients with an estimated glomerular filtration rate of 29 mL per minute or less, 6 required dose reductions attributable to myelosuppression (n = 3) or to worsening renal function (n = 3). The overall survival (OS) at 18 months was 12%, and the median OS was 8.6 months.


CONCLUSIONS
The use of HA in patients with RI is feasible, but is associated with a higher incidence of toxicity. Dose adjustments and the use of growth factor may be necessary for some patients.
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
G Nicolas
GN
Batty
Hagop
H
Kantarjian
Jean-Pierre
JP
Issa
Elias
E
Jabbour
Fabio P S
FP
Santos
Deborah
D
McCue
Guillermo
G
Garcia-Manero
Sherry
S
Pierce
Susan
S
O'Brien
Jorge E
JE
Cortés
Farhad
F
Ravandi
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001374:Azacitidine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000077209:Decitabine; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects*; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy; D015477:Leukemia, Myelomonocytic, Chronic / Q000150:complications / Q000188:drug therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy; D051437:Renal Insufficiency / Q000150:complications*
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine