Maximum Plasma Concentration of Lenvatinib Is Useful for Predicting Thrombocytopenia in Patients Treated for Hepatocellular Carcinoma

Mizuki Endo, Koichi Honda, Tomoko Saito, Ken Shiraiwa, Yoshio Sueshige, Tomoko Tokumaru, Masao Iwao, Masanori Tokoro, Mie Arakawa, Ryota Tanaka, Ryosuke Tatsuta, Masataka Seike, Hiroki Itoh, Kazunari Murakami

Abstract


Background: Although lenvatinib treatment has a favorable efficacy for unresectable hepatocellular carcinoma (HCC), it is associated with adverse events (AEs) that must be closely monitored and managed. Thrombocytopenia is one of the major AEs. The aim of this study was to clarify whether thrombocytopenia can be predicted by the plasma concentration of lenvatinib.

Methods: This was a single-center retrospective observational study. Twenty-three patients with unresectable HCC and pharmacokinetics data at the initial lenvatinib administration between May 2018 and September 2020 at Oita University Hospital were enrolled. The AEs during the 4 weeks after the initiation of treatment were evaluated, and the correlations between the thrombocytopenia and the plasma concentration of lenvatinib were examined. Spearmans correlation was used to evaluate the correlation between two continuous variables.

Results: The rate of platelet count decrease correlated with the maximum plasma concentration (Cmax) (r = 0.65, P = 0.001), whereas it did not with the minimum plasma concentration (Cmin) (r = 0.29, P = 0.206). After stepwise multiple linear regression analysis, the starting dose of lenvatinib and the serum albumin concentration were identified as independent explanatory variables. Next, a formula for predicting the Cmax using these two variables was created. The predicted Cmax was strongly correlated with the Cmax (r = 0.87, P < 0.0001) and the rate of platelet count decrease (r = 0.67, P = 0.001).

Conclusions: This study identified the usefulness of the drug Cmax to predict the rate of platelet count decrease within 4 weeks after the initiation of treatment. Although it is difficult to measure the plasma concentration of lenvatinib in community hospitals, the predicted Cmax is useful for predicting the rate of platelet count decrease with this treatment.




World J Oncol. 2021;12(5):165-172
doi: https://doi.org/10.14740/wjon1399

Keywords


Hepatocellular carcinoma; Lenvatinib; Plasma concentration; Thrombocytopenia

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