title: Analysis of adverse events associated with dasatinib and nilotinib treatments in chronic-phase chronic myeloid leukemia patients outside clinical trials.
abstract: We analyzed adverse events (AEs) in 201 chronic phase CML patients treated with nilotinib (n = 120) or dasatinib (n = 81) as first- or second-line therapy. The dasatinib group had significantly higher grade 3-4 AEs compared to the nilotinib group (22 vs. 54%, p < 0.001), and had more frequent dose reduction, interruption, and discontinuation (p < 0.001, p = 0.004, and p = 0.006, respectively). Of 59 patients who discontinued treatment, 47 (80%) discontinued treatment due to AEs; 50% of the AEs causing drug discontinuation were of grade 2 severity. Compared to the second-line setting, discontinuation occurred more rapidly in the first-line setting (2.9 vs. 15.6 months, p = 0.015). Pleural effusion occurred in 35% (28/81) of the patients with dasatinib and led to dasatinib discontinuation in 14 patients (grade 2 of 79%). Pulmonary artery hypertension occurred in one patient with dasatinib. Stroke, acute coronary syndrome, and peripheral artery occlusive disease occurred in 5% (6/120) of the patients treated with nilotinib. The dasatinib group had shorter event-free survival than nilotinib group (first-line, p = 0.051; second-line, p = 0.025). In the clinical practice setting, nilotinib or dasatinib use was more frequently interrupted than recommended by guidelines in association with less severe AEs. We believe this phenomenon is attributable to the availability of other TKIs.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-di, 13620, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
authors.forename: Koung Jin
authors.initials: KJ
authors.lastname: Suh
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-di, 13620, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-di, 13620, Korea.
authors.forename: Soo-Mee
authors.initials: SM
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea. ihkimmd@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. ihkimmd@snu.ac.kr.
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-di, 13620, Korea. jeongok77@gmail.com.
authors.forename: Jeong-Ok
authors.identifier: http://orcid.org/0000-0001-9402-6372
authors.initials: JO
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D000069439:Dasatinib / Q000009:adverse effects*; D000069340:Deprescriptions; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000139:chemically induced* / Q000453:epidemiology; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects*; D015996:Survival Rate; D014652:Vascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib
keywords: Dasatinib; Discontinuation; Nilotinib; Pleural effusion; Toxicity