PMID- 37886165
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231028
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Planned drug holidays during treatment with lenvatinib for radioiodine-refractory 
      differentiated thyroid cancer: a retrospective study.
PG  - 1139659
LID - 10.3389/fonc.2023.1139659 [doi]
LID - 1139659
AB  - BACKGROUND: In the phase 3 SELECT study, lenvatinib significantly improved 
      prognostic outcomes vs. placebo in patients with radioiodine-refractory 
      differentiated thyroid cancer (RR-DTC). However, toxicity of lenvatinib is 
      sometimes considerable and requires frequent dose interruptions and 
      modifications. Recently, planned drug holidays have been proposed as a means of 
      avoiding severe adverse events (AEs). METHODS: We retrospectively reviewed 
      medical records to compare the efficacy and safety of lenvatinib in RR-DTC 
      patients who underwent planned drug holidays (planned holiday group) vs. those 
      who received conventional daily oral administration (daily group). RESULTS: The 
      subjects were 25 patients in the planned holiday group and 21 in the daily group. 
      Median age was 73 years (range 43-84) and 62 years (range 42-75), and histologic 
      subtype of papillary/follicular was 21/4 cases and 15/6 cases, respectively. Time 
      to treatment failure (TTF) and overall survival (OS) were significantly longer in 
      the planned holiday group than the daily group (not reached [NR] vs. 14.9 months, 
      hazard ratio [HR] 0.25, 95% confidence interval [Cl] 0.11-0.58, p<0.001; NR vs. 
      26.6 months, HR 0.20, 95% CI 0.073-0.58, p=0.001, respectively). Median 
      progression-free survival (PFS) was NR in the planned holiday group vs. 15.1 
      months in the daily group (HR 0.31, 95% CI 0.14-0.68, p=0.002). Duration of the 
      period with lenvatinib dose >/=10 mg was significantly longer in the planned 
      holiday group (NR vs. 6.5 months, HR 0.22, 95% CI 0.10-0.49, p<0.001), and the 
      frequency of drug interruption due to intolerable AEs was lower (68.0% vs. 95.2%, 
      p=0.027). CONCLUSION: Planned drug holidays for lenvatinib demonstrated 
      significantly longer PFS, TTF, and OS than daily oral administration, and less 
      intolerable toxicity leading to further unplanned treatment interruption. These 
      benefits were apparently associated with a more extended period of lenvatinib 
      administration at >/=10 mg. These findings might contribute to a favorable patient 
      prognosis and safer toxicity profile.
CI  - Copyright (c) 2023 Matsuyama, Enokida, Ueda, Suzuki, Fujisawa, Ito, Okano and 
      Tahara.
FAU - Matsuyama, Chihiro
AU  - Matsuyama C
AD  - Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Japan.
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Kyoto, Japan.
FAU - Enokida, Tomohiro
AU  - Enokida T
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
FAU - Ueda, Yuri
AU  - Ueda Y
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Tokyo Medical 
      University, Shinjuku, Japan.
FAU - Suzuki, Shinya
AU  - Suzuki S
AD  - Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Japan.
FAU - Fujisawa, Takao
AU  - Fujisawa T
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
FAU - Ito, Kazue
AU  - Ito K
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
AD  - Department of Head and Neck Medical Oncology, Miyagi Cancer Center, Natori, 
      Japan.
FAU - Okano, Susumu
AU  - Okano S
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
FAU - Tahara, Makoto
AU  - Tahara M
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
LA  - eng
PT  - Journal Article
DEP - 20231011
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10598871
OTO - NOTNLM
OT  - VEGF tyrosine kinase inhibitor
OT  - adverse events
OT  - lenvatinib
OT  - oral anticancer agent
OT  - planned drug holidays
OT  - thyroid cancer
COIS- MT reports grants and personal fees from Eisai during the conduct of the study; 
      and grants and personal fees from Ono Pharmaceutical, BMS, Bayer, MSD, Eli Lilly, 
      GSK, Pfizer, AstraZeneca, Rakuten Medical and Merck Biopharma, grants from 
      Novartis, and personal fees from Boehringer Ingelheim and Genmab outside the 
      submitted work. SO received honoraria from Ono Pharmaceutical, Bristol-Myers 
      Squibb, MSD, Merck Biopharma and Meiji Sika Pharma. YU received honoraria from 
      Bristol-Myers Squibb. The remaining authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2023/10/27 06:43
MHDA- 2023/10/27 06:44
PMCR- 2023/01/01
CRDT- 2023/10/27 04:33
PHST- 2023/01/07 00:00 [received]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2023/10/27 06:44 [medline]
PHST- 2023/10/27 06:43 [pubmed]
PHST- 2023/10/27 04:33 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1139659 [doi]
PST - epublish
SO  - Front Oncol. 2023 Oct 11;13:1139659. doi: 10.3389/fonc.2023.1139659. eCollection 
      2023.