PMID- 32325921
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 4
DP  - 2020 Apr 19
TI  - Weekends-Off Lenvatinib for Unresectable Hepatocellular Carcinoma Improves 
      Therapeutic Response and Tolerability toward Adverse Events.
LID - 10.3390/cancers12041010 [doi]
LID - 1010
AB  - Background: Although lenvatinib has become the standard therapy for 
      hepatocellular carcinoma (HCC), the high incidence rate of adverse events (AEs) 
      is an issue. This study aimed to clarify the AEs of lenvatinib and the 
      therapeutic impact of five days-on/two days-off administration (i.e., 
      weekends-off strategy) for lenvatinib. Methods: We retrospectively assessed the 
      therapeutic effects and AEs of 135 patients treated with lenvatinib, and the 
      improvement of tolerability and therapeutic efficacy of 30 patients treated with 
      the weekends-off strategy. We also evaluated lenvatinib-induced vascular changes 
      in tumors and healthy organs using a mouse hepatoma model. Results: The incidence 
      rates of any grade and grade >/= 3 AEs were 82.1% and 49.6%. Fatigue was the most 
      important AE since it resulted in dose reduction and discontinuation. Of the 30 
      patients who received weekends-off lenvatinib, 66.7% tolerated the AEs. Although 
      80.8% of the patients showed progression after dose reduction, the therapeutic 
      response improved in 61.5% of the patients by weekends-off lenvatinib. Notably, 
      weekends-off administration significantly prolonged the administration period and 
      survival (p < 0.001 and p < 0.05). The mouse hepatoma model showed that 
      weekends-off administration contributed to recovery of vascularity in the organs. 
      Conclusion: Weekends-off administration of lenvatinib was useful to recover the 
      therapeutic response and tolerability toward AEs.
FAU - Iwamoto, Hideki
AU  - Iwamoto H
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
AD  - Iwamoto Internal Medicine Clinic, Kitakyusyu 802-0832, Japan.
FAU - Suzuki, Hiroyuki
AU  - Suzuki H
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Shimose, Shigeo
AU  - Shimose S
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Niizeki, Takashi
AU  - Niizeki T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Nakano, Masahito
AU  - Nakano M
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Shirono, Tomotake
AU  - Shirono T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Okamura, Shusuke
AU  - Okamura S
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Noda, Yu
AU  - Noda Y
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Kamachi, Naoki
AU  - Kamachi N
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Nakamura, Toru
AU  - Nakamura T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Masuda, Atsutaka
AU  - Masuda A
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Sakaue, Takahiko
AU  - Sakaue T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Tanaka, Toshimitsu
AU  - Tanaka T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Nakano, Dan
AU  - Nakano D
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Sakai, Miwa
AU  - Sakai M
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Yamaguchi, Taizo
AU  - Yamaguchi T
AD  - Iwamoto Internal Medicine Clinic, Kitakyusyu 802-0832, Japan.
FAU - Kuromatsu, Ryoko
AU  - Kuromatsu R
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Koga, Hironori
AU  - Koga H
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
FAU - Torimura, Takuji
AU  - Torimura T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume 830-0011, Japan.
LA  - eng
GR  - 18K15831/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20200419
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7226076
OTO - NOTNLM
OT  - adverse events
OT  - hepatocellular carcinoma
OT  - lenvatinib
OT  - molecular targeted agents
OT  - weekends-off
COIS- The authors declare no potential conflicts of interest.
EDAT- 2020/04/25 06:00
MHDA- 2020/04/25 06:01
PMCR- 2020/04/19
CRDT- 2020/04/25 06:00
PHST- 2020/03/13 00:00 [received]
PHST- 2020/04/08 00:00 [revised]
PHST- 2020/04/16 00:00 [accepted]
PHST- 2020/04/25 06:00 [entrez]
PHST- 2020/04/25 06:00 [pubmed]
PHST- 2020/04/25 06:01 [medline]
PHST- 2020/04/19 00:00 [pmc-release]
AID - cancers12041010 [pii]
AID - cancers-12-01010 [pii]
AID - 10.3390/cancers12041010 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Apr 19;12(4):1010. doi: 10.3390/cancers12041010.