Second Generation Tyrosine Kinase Inhibitors and Their Toxicity in Treatment of Patients in Chronic Phase of Chronic Myeloid Leukemia

N.S. Lazorko1, E.G. Lomaia1, E.G. Romanova1, E.I. Sbityakova1, E.R. Machyulaitene2, P.A. Butylin1,3, A.Yu. Zaritskii1,2

1 Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russia, 197341

2 Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russia, 197022

3 Saint Petersburg State University of Information Technologies, Mechanics and Optics, Institute of Translational Medicine, 49 Kronverkskii pr-t, Saint Petersburg, Russia, 197101

For correspondence: Elza Galaktionovna Lomaia, PhD, 2 Akkuratova str., Saint Petersburg, Russia, 197341; Tel.: +7(812)702-37-65; e-mail:

For citation: Lazorko N.S., Lomaia E.G., Romanova E.G., Sbityakova E.I., Machyulaitene E.R., Butylin P.A., Zaritskii A.Yu. Second Generation Tyrosine Kinase Inhibitors and Their Toxicity in Treatment of Patients in Chronic Phase of Chronic Myeloid Leukemia. Klin. Onkogematol. 2015;8(3):302–8. (In Russ.)


Background & Aims. Certain experience in the use of new tyrosine kinase inhibitors (TKIs) in treatment of patients with chronic myeloid leukemia has been obtained over the last years. The article summarizes literature data on toxicity obtained in international clinical trials. The aim of the study is to evaluate adverse effects of second generation TKIs in the routine clinical practice and to assess their effect on patient future life.

Methods. We analyzed our own data obtained during routine clinical practice. 76 patients (36 men and 40 women) over 18 years of age (median age was 49 years, range 26–75) with chronic myeloid leukemia were enrolled in the retrospective trial. 48 patients were treated with nilotinib, 28 patients received dazatinib during the chronic phase of the disease as a second line therapy after withdrawal of imatinib mesylate. The toxicity degree was determined according to CTCAE 4.0 criteria.

Results. III–IV degree hematologic toxicity was registered in 36.8 % of patients. No significant difference in the incidence of complications between nilotinib and dazatinib groups was observed: 39.6 % and 32.1 %, respectively. II–IV degree non-hematologic toxicity was found in 35.4 % patients on nilotinib and in 25 % of patients on dazatinib. The incidence of individual types of toxicity did not exceed 15 %. A combination of different types of non-hematologic toxicity was observed in 9.2 % of patients. No TKI2 toxicity-related lethal outcomes were registered.

Conclusion. Hematologic and/or non-hematologic toxicity related to TKI2 was registered in more than 50 % of patients. In most cases, the complications were transient and eliminated after discontinuation of TKI2 or after dose reduction. TKI2-associated complications did not affect the possibility to achieve a complete cytogenetic response and its stability.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, toxicity.

Received: January 29, 2015

Accepted: June 1, 2015

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