TY - JOUR
T1 - Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma
AU - Hata, Kojiro
AU - Suetsugu, Kimitaka
AU - Egashira, Nobuaki
AU - Makihara, Yoko
AU - Itoh, Shinji
AU - Yoshizumi, Tomoharu
AU - Tanaka, Masatake
AU - Kohjima, Motoyuki
AU - Watanabe, Hiroyuki
AU - Masuda, Satohiro
AU - Ieiri, Ichiro
N1 - Funding Information:
The present study was funded in part by a Grant-in-Aid for Scientific Research (KAKENHI) from the Japanese Society for the Promotion of Science (JSPS, grant number JP20K16078). Acknowledgements
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Purpose: This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). Methods: Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (Ctrough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the Ctrough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). Results: The Ctrough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-Ctrough median group (≥ 42.68 ng/mL) than in the low-Ctrough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-Ctrough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-Ctrough median group than in the low-Ctrough median group. Multivariate analysis showed that high-Ctrough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63–138.16; p = 0.0168). Conclusion: Maintaining Ctrough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.
AB - Purpose: This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). Methods: Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (Ctrough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the Ctrough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). Results: The Ctrough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-Ctrough median group (≥ 42.68 ng/mL) than in the low-Ctrough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-Ctrough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-Ctrough median group than in the low-Ctrough median group. Multivariate analysis showed that high-Ctrough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63–138.16; p = 0.0168). Conclusion: Maintaining Ctrough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.
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U2 - 10.1007/s00280-020-04178-x
DO - 10.1007/s00280-020-04178-x
M3 - Article
C2 - 33095285
AN - SCOPUS:85093963508
VL - 86
SP - 803
EP - 813
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 6
ER -