BPB Reports

Paper Details

BPB Reports
Vol. 7 No. 4 p.132-140 2024
Regular Article
Adverse Effects Induced by Osimertinib Based on the Dose per Body Constitutional Parameters: A Retrospective Observational Study
  • Yuji Hotta (Department of Hospital Pharmacy, Nagoya City University Graduate School of Pharmaceutical Sciences / Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences / Department of Pharmacy, Nagoya City University Hospital / yhotta@med.nagoya-cu.ac.jp)
Masaya Nagamizu 1) 2) , Yuji Hotta 1) 3) 4) , Issei Morozumi 2) , Daigaku Nakamura 4) , Masayuki Hori 4) , Yuto Otsuka 4) , Ryuhei Takemoto 4) , Yasuhiro Horita 3) 4) , Eri Wakita 5) , Nobuyuki Morishita 2) , Masahiro Kondo 3) 5) , Yoko Furukawa‐Hibi 3) 4) , Kazunori Kimura 1) 3) 4)
1) Department of Hospital Pharmacy, Nagoya City University Graduate School of Pharmaceutical Sciences , 2) Department of Pharmacy, Nagoya City University West Medical Center , 3) Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences , 4) Department of Pharmacy, Nagoya City University Hospital , 5) Department of Pharmacy, Nagoya City University East Medical Center
Received: June 04, 2024;   Accepted: August 10, 2024;   Released: August 22, 2024
Keywords: osimertinib, body constitutional parameters, body surface area, lean body mass, adverse event
Abstracts

Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor treatment for non-small-cell lung cancer. Area under the blood concentration-time curve (AUC) of osimertinib can be related to the development of adverse events (AEs). Furthermore, the dose-per-body constitutional parameters (BCPs), such as body weight, body surface area (BSA), or lean body mass (LBM), are closely related to the AUC. However, BCPs other than weight have not been considered in clinical trials. Therefore, in this retrospective study, we investigated the association between doses per BCP (Dose/BCPs) and AEs of osimertinib. Method: Forty-two patients who received osimertinib between January 2010 and December 2020 were investigated. Differences in Dose/BCPs were compared between patients with and without AEs. Results: Among the patients, 54.8%, 38.1%, and 28.6% developed thrombocytopenia, neutropenia, and leukopenia, respectively. The Dose/BSA and Dose/LBM were significantly higher in patients who developed leukopenia than in those who did not (p < 0.05). The cutoff values of Dose/BSA and Dose/LBM associated with leukopenia were 50.0 mg/m2 and 1.86 mg/kg, respectively. Conclusion: This study suggests that Dose/BCPs are associated with the development of leukopenia. Now, fixed dose regardless of BCPs is approved on almost of oral molecular targeting agents. However, the patients with low BCPs can be also received these medications in clinical practices. Therefore, although the sample size is small, the results of this study suggests the potential risk on the fixed dose. Moreover, Dose/BSA or Dose/LBM may be a useful parameter for assessing the risk of leukopenia with osimertinib.