A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine

Abstract

Purpose

There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater.

Methods

We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min).

Results

Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43).

Conclusions

This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Keywords

Decitabine acute myeloid leukemia renal impairment toxicity

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References

Cancer Statistics Review, 1975-2013 -–SEER Statistics Seer.cancer.gov. 2016, http://seer.cancer.gov/csr/1975_2013/ (accessed 17 June 2016).

National Comprehensive Cancer Network. Acute Myeloid Leukemia (Version 2.2014), http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf (accessed 20 October 2014).

Cashen

Schiller

O'Donnell

et al.

Multicenter, Phase II Study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol 2009; 28: 556–561.

Kantarjian

Thomas

Dmoszynska

et al.

Multicenter, Randomized, Open-Label, Phase III Trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012; 30: 2670–2677.

Blum

Garzon

Klisovic

et al.

Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci 2010; 107: 7473–7478.

Bryan

Kantarjian

Garcia-Manero

et al.

Pharmacokinetic evaluation of decitabine for the treatment of leukemia. Expert Opin Drug Metab Toxicol 2011; 7: 661–672.

Product Information: DACOGEN® injection, decitabine injection. Woodcliff Lake, NJ: Eisai, Inc, 2010.

Rogstad

Herring

Theruvathu

et al.

Chemical decomposition of 5-Aza-2′-deoxycytidine (decitabine): kinetic analyses and identification of products by NMR, HPLC, and mass spectrometry. Chem Res Toxicol 2009; 22: 1194–1204.

Lubbert

Ruter

Claus

et al.

A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy. Haematologica 2011; 97: 393–401.

10.

Batty

Kantarjian

Issa

et al.

Feasibility of therapy with hypomethylating agents in patients with renal insufficiency. Clin Lymphoma Myeloma Leukemia 2010; 10: 205–210.

11.

Sorror

. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.