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- Title
Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC.
- Authors
Qian Zhu; Hao Hu; De-Sheng Weng; Xiao-Fei Zhang; Chang-Long Chen; Zi-Qi Zhou; Yan Tang; Jian-Chuan Xia; Zhu, Qian; Hu, Hao; Weng, De-Sheng; Zhang, Xiao-Fei; Chen, Chang-Long; Zhou, Zi-Qi; Tang, Yan; Xia, Jian-Chuan
- Abstract
<bold>Background: </bold>The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear.<bold>Methods: </bold>We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials. Severe adverse events (AEs) (grade ≥ 3) based on the ALK-TKI type were analysed.<bold>Results: </bold>Seventeen trials published between 2011 and 2016, including a total of 1826 patients, were eligible for analysis. Patients in 10 trials (n = 1000) received crizotinib, patients in 5 trials (n = 601) received ceritinib and patients in 2 trials (n = 225) received alectinib. The overall frequencies of treatment-related death and AEs due to treatment withdrawal were 0.9% (12/1365) and 5.5% (85/1543), respectively. Moreover, the frequency of severe AEs in patients treated with ceritinib was significantly higher than patients treated with crizotinib or alectinib, especially for hepatotoxicity, fatigue and some of gastrointestinal symptoms. Additionally, significant difference in the elevated lipase and amylase levels (grade ≥ 3) were detected between ceritinib and crizotinib/alectinib, whereas neutropenia was less frequent.<bold>Conclusions: </bold>ALK-TKIs were safe for ALK-positive patients. Moreover, statistically significant differences in some severe AEs among ceritinib, crizotinib and alectinib were detected in present study.
- Subjects
CANCER treatment; NON-small-cell lung carcinoma; ANAPLASTIC lymphoma kinase; PROTEIN-tyrosine kinase inhibitors; ADVERSE health care events; CRIZOTINIB; DRUG toxicity; THERAPEUTICS; CLINICAL trials; COMPARATIVE studies; HETEROCYCLIC compounds; LUNG cancer; LUNG tumors; RESEARCH methodology; MEDICAL cooperation; META-analysis; PATIENT safety; PIPERIDINE; PYRIDINE; RESEARCH; SULFONES; TRANSFERASES; SYSTEMATIC reviews; EVALUATION research; PROTEIN kinase inhibitors
- Publication
BMC Cancer, 2017, Vol 17, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-017-3405-3