Serum concentration of the CKD4/6 inhibitor abemaciclib, but not of creatinine, strongly predicts hematological adverse
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SHORT REPORT
Serum concentration of the CKD4/6 inhibitor abemaciclib, but not of creatinine, strongly predicts hematological adverse events in patients with breast cancer: a preliminary report Akimitsu Maeda 1 & Kei Irie 2,3 & Naoya Hashimoto 1 & Shoji Fukushima 2 & Hitoshi Ando 4 & Akira Okada 5 & Hiromichi Ebi 6 & Masaki Kajita 1 & Hiroji Iwata 7 & Masataka Sawaki 7 Received: 25 June 2020 / Accepted: 24 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Purpose The CKD4/6 inhibitor abemaciclib is related to adverse events such as hematological toxicity and increase in serum creatinine levels associated with abemaciclib pharmacokinetics. Increase in serum creatinine levels is considered a result of competition with abemaciclib via organic cation transporter 2 and multidrug and toxic compound extrusion. Therefore, we evaluated the association among serum creatinine levels, serum abemaciclib concentrations, and adverse events and whether increase in serum creatinine levels is a useful indicator for predicting the onset of the adverse events of abemaciclib. Methods In total, the data of 12 patients with breast cancer who were treated with abemaciclib (150 mg twice daily) were evaluated to determine the association between increased serum creatinine levels and abemaciclib concentrations and hematological toxicity. Results Grade 3 neutropenia, thrombocytopenia, and anemia were observed at 4 weeks in four (33%), two (17%), and one (8%) patients, respectively. A significant association was observed between steady-state abemaciclib concentrations and the rate of decrease in neutrophil and platelet counts (r = − 0.80, P = 0.003 and r = − 0.70, P = 0.016, respectively). Compared with baseline levels (0.61 [0.53–0.82] mg/mL), serum creatinine levels significantly increased and reached a steady state in at least 2 weeks (0.84 [0.61–1.02] mg/mL, P = 0.01). However, we did not find a significant association between increase in serum creatinine levels and abemaciclib concentrations and hematological toxicity. Conclusions Abemaciclib concentrations are associated with neutropenia and thrombocytopenia. However, increase in serum creatinine levels may not be a useful predictor for estimating abemaciclib pharmacokinetics and hematological toxicity. Keywords Abemaciclib . Creatinine . Pharmacokinetics . Adverse event
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-00994-3) contains supplementary material, which is available to authorized users. * Akimitsu Maeda [email protected]
4
Department of Cellular and Molecular Function Analysis, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan
1
Department of Pharmacy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Aichi Nagoya 464-8681, Japan
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Department of Regulatory Science, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi , Nishitokyo City 202-8585, Japan
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Department of Pharmaceutics, Faculty of P
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