Intravoxel incoherent motion MRI for monitoring the therapeutic response of hepatocellular carcinoma to sorafenib treatment in mouse xenograft tumor models

2016 ◽  
Vol 58 (9) ◽  
pp. 1045-1053 ◽  
Author(s):  
Yedaun Lee ◽  
Seung Soo Lee ◽  
Hyunhee Cheong ◽  
Chang Kyung Lee ◽  
Namkug Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Diffusion Coefficient ◽  
Therapeutic Response ◽  
Post Treatment ◽  
Control Group ◽  
Therapeutic Effects ◽  
Tumor Cell Death ◽  
Mouse Xenograft ◽  
Tumor Periphery

Background With the introduction of targeted therapies, there has been a growing need for non-invasive imaging methods which accurately evaluate therapeutic effects and overcome the limitations of tumor size-based therapeutic response assessments. Purpose To assess diagnostic values of intra-voxel incoherent motion (IVIM) imaging in evaluating therapeutic effects of sorafenib on hepatocellular carcinoma (HCC) using mouse xenograft model. Material and Methods Twenty-four mice bearing Huh-7 were divided into a control group and two treatment groups received sorafenib doses of 5 mg/kg (5 mg-Tx) or 30 mg/kg (30 mg-Tx). IVIM imaging was performed using 10 b-values (0–900 s/mm2). The apparent diffusion coefficient (ADC), diffusion coefficient ( D), and perfusion fraction ( f) were measured for whole tumors and tumor periphery. Changes between baseline and post-treatment parameters ( Δ ADC, Δ D, and Δ f) were calculated, and these parameters were compared with microvessel density (MVD) and area of tumor cell death. Results The post-treatment f and Δ f for tumor periphery were significantly higher in control group, followed by 5 mg-Tx and 30 mg-Tx ( P < 0.001). MVD showed significant positive correlation with post-treatment f ( r = 0.584, P = 0.003) and negative correlation with D ( r = –0.495, P = 0.014) for tumor periphery, while no parameter showed significant correlation with area of tumor cell death. Conclusion The f is significantly correlated with MVD of HCC, and could potentially be used to evaluate the anti-angiogenic effects of sorafenib.

scholarly journals Therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma using contrast-enhanced ultrasound: Focusing on inter-scanner, and inter-operator reproducibility

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244304
Author(s):  
Hwaseong Ryu ◽  
Jung Hoon Kim ◽  
Seunghyun Lee ◽  
Joon Koo Han
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Treatment Group ◽  
Rat Model ◽  
Therapeutic Response ◽  
Response Monitoring ◽  
Control Group ◽  
Rat Models ◽  
Significant Change ◽  
Operator Reproducibility

Purpose To assess therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) using CEUS with focusing on inter-scanner and inter-operator reproducibility. Materials and methods For reproducibility, CEUS was performed using two different US scanners by two operators in sixteen rat models of HCC. Using perfusion analysis software (VueBox ®), eleven parameters were collected, and intra-class correlation coefficient (ICC) was used to analyze reproducibility. Then seventeen rat models of HCC were divided into treatment group (n = 8, 30 mg/kg/day sorafenib for five days) and control group (n = 9). CEUS was performed at baseline and 14 days after first treatment, and changes of perfusion parameters were analyzed. Results In treatment group, CEUS perfusion parameters showed a significant change. The peak enhancement (PE, 2.50 x103±1.68 x103 vs 5.55x102±4.65x102, p = 0.010) and wash-in and wash out AUC (WiWoAUC, 1.07x105±6.48 x104 vs 2.65x104±2.25x104, p = 0.009) had significantly decreased two weeks after treatment. On the contrary, control group did not show a significant change, including PE (1.15 x103±7.53x102 vs 9.43x102± 7.81 x102, p = 0.632) and WiWoAUC (5.09 x104±3.25x104 vs 5.92 x104±3.20x104, p = 0.646). For reproducibility, the various degrees of inter-scanner reproducibility were from poor to good (ICC: <0.01–0.63). However, inter-operator reproducibility of important perfusion parameters, including WiAUC, WoAUC, and WiWoAUC, ranged from fair to excellent (ICC: 0.59–0.93) in a different scanner. Conclusion Our results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.

scholarly journals Metastasis-Associated Protein 1 Is Involved in Angiogenesis after Transarterial Chemoembolization Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Tao Xue ◽  
Wenming Feng ◽  
Hongbin Yu ◽  
Ming Zhu ◽  
Maoyun Fei ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Hypoxia Inducible Factor ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Therapeutic Effects ◽  
Arterial Blood ◽  
Tumor Periphery ◽  
Before And After ◽  
Tace Treatment

Background. Transarterial chemoembolization (TACE), a well-established treatment for unresectable hepatocellular carcinoma (HCC), blocks the arterial blood supply to the tumor, which can be short-lived as development of collateral neovessels, leading to the failure of treatment. Metastasis-associated protein 1 (MTA1) is involved in development of tumors and metastases. However, the role of MTA1 in angiogenesis is still obscure. Methods. We detected the expression of MTA1 and hypoxia-inducible factor-1α (HIF-1α) and microvessel density (MVD) value in liver tumor tissues and tumor periphery before and after TACE treatment. Hepatocellular carcinoma cell line HepG2, tube formation assay, and chorioallantoic membrane (CAM) assay were applied to explore the mechanism of MTA1 in angiogenesis. Results. We found that expression of MTA1 increased after TACE treatment, especially in tumor periphery, which was accompanied by markedly elevated MVD value, indicating a significant correlation between MTA1 and MVD value. Moreover, MTA1 contributed to neovascularization of residual tumors. Cellular experiments further revealed that MTA1 increased the stability and the expression of HIF-1α, and overexpression of MTA1 enhanced tube formation and neovessels of chick embryos. Conclusions. MTA1 is an active angiogenic regulator; our results shed light on better understanding in neovascularization, which are helpful to predict prognosis of TACE, and provide evidences for intervention to improve therapeutic effects on HCC.

scholarly journals Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study

2020 ◽  
Author(s):  
Abdullah Fatih Demirci ◽  
Coskun Ozer Demirtas ◽  
Fatih Eren ◽  
Demet Yilmaz ◽  
Caglayan Keklikkiran ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Turkish Population ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Programmed Cell Death 1 ◽  
Significant Difference ◽  
And Control

Background and Aims: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. Methods: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. Results: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). Conclusion: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

scholarly journals RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 167-174
Author(s):  
Ninzi Tian ◽  
Dong Wu ◽  
Ming Tang ◽  
Huichuan Sun ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Response ◽  
Therapeutic Effects ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Expression Levels ◽  
Portal Vein Flow ◽  
Tumor Tissues ◽  
Resistant Group

AbstractObjectivesMonitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.MethodsA total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.ResultsAccording to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.ConclusionRAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

scholarly journals A Novel Chimeric Oncolytic Virus Vector for Improved Safety and Efficacy as a Platform for the Treatment of Hepatocellular Carcinoma

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Sarah Abdullahi ◽  
Melanie Jäkel ◽  
Sabine J. Behrend ◽  
Katja Steiger ◽  
Geoffrey Topping ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Safety Profile ◽  
Oncolytic Virus ◽  
Envelope Proteins ◽  
Oncolytic Viruses ◽  
Response To Treatment ◽  
Therapeutic Effects ◽  
Immunogenic Cell Death ◽  
Wild Type

ABSTRACT Oncolytic viruses represent an exciting new aspect of the evolving field of cancer immunotherapy. We have engineered a novel hybrid vector comprising vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV), named recombinant VSV-NDV (rVSV-NDV), wherein the VSV backbone is conserved but its glycoprotein has been replaced by the hemagglutinin-neuraminidase (HN) and the modified, hyperfusogenic fusion (F) envelope proteins of recombinant NDV. In comparison to wild-type VSV, which kills cells through a classical cytopathic effect, the recombinant virus is able to induce tumor-specific syncytium formation, allowing efficient cell-to-cell spread of the virus and a rapid onset of immunogenic cell death. Furthermore, the glycoprotein exchange substantially abrogates the off-target effects in brain and liver tissue associated with wild-type VSV, resulting in a markedly enhanced safety profile, even in immune-deficient NOD.CB17-prkdcscid/NCrCrl (NOD-SCID) mice, which are highly susceptible to wild-type VSV. Although NDV causes severe pathogenicity in its natural avian hosts, the incorporation of the envelope proteins in the chimeric rVSV-NDV vector is avirulent in embryonated chicken eggs. Finally, systemic administration of rVSV-NDV in orthotopic hepatocellular carcinoma (HCC)-bearing immune-competent mice resulted in significant survival prolongation. This strategy, therefore, combines the beneficial properties of the rapidly replicating VSV platform with the highly efficient spread and immunogenic cell death of a fusogenic virus without risking the safety and environmental threats associated with either parental vector. Taking the data together, rVSV-NDV represents an attractive vector platform for clinical translation as a safe and effective oncolytic virus. IMPORTANCE The therapeutic efficacy of oncolytic viral therapy often comes as a tradeoff with safety, such that potent vectors are often associated with toxicity, while safer viruses tend to have attenuated therapeutic effects. Despite promising preclinical data, the development of VSV as a clinical agent has been substantially hampered by the fact that severe neurotoxicity and hepatotoxicity have been observed in rodents and nonhuman primates in response to treatment with wild-type VSV. Although NDV has been shown to have an attractive safety profile in humans and to have promising oncolytic effects, its further development has been severely restricted due to the environmental risks that it poses. The hybrid rVSV-NDV vector, therefore, represents an extremely promising vector platform in that it has been rationally designed to be safe, with respect to both the recipient and the environment, while being simultaneously effective, both through its direct oncolytic actions and through induction of immunogenic cell death.

Therapeutic Effects of Moxibustion on Experimental Tumor

1999 ◽  
Vol 27 (02) ◽  
pp. 157-166 ◽  
Author(s):  
Dou-Mong Hau ◽  
I-Hsin Lin ◽  
Jaung-Geng Lin ◽  
Yung-Hsich Chang ◽  
Ching-Ha Lin
Keyword(s):  
Therapeutic Response ◽  
Subcutaneous Tissue ◽  
Tumor Therapy ◽  
Radioactive Tracer ◽  
Control Group ◽  
Therapeutic Effects ◽  
Experimental Tumor ◽  
Mean Survival Time ◽  
Reliable Model ◽  
Experimental Group

This work investigated the therapeutic effects of the improved form of moxibustion (MT) on experimental tumor. Sarcoma 180 cells (1 × 107) were transplanted into the subcutaneous tissue in the breast area of female ICR mice. Mice bearing a tumor were divided into one control and four experimental groups. The experimental groups were treated with MT for 1, 2, 3 and 4 times (abbreviated as MT1, MT2, MT3, MT4, respectively). This study showed that the experimental group treated with MT3 displayed the optimal therapeutic response. The longest mean survival time (87.8 days) within 120 days after treatment of MT3 significantly differed from the control group (60.2 days). In addition, uptake of 86Rb-radioactive tracer significantly decreased in tumors treated with MT3. The improved form of moxibustion used in this study is a reliable model of localized hyperthermia in tumor therapy.

scholarly journals CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1793
Author(s):  
Li-Yun Fann ◽  
Jui-Hu Shih ◽  
Jen-Ho Tseng ◽  
Hsu-Shan Huang ◽  
Sheng-Huang Hsiao
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Cell Lines ◽  
Mtt Assay ◽  
Xenograft Model ◽  
Tumor Cell Death ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potential anti-GBM effects in two GBM cell lines, U87MG and U118MG. The observations of cell morphology, MTT assay, flow cytometry-based apoptosis after CC12 treatment, were conducted. Western blot was performed for the investigation of the apoptotic mechanism. Positron emission tomography scan analysis and bioluminescent imaging assay using a mouse xenograft model were performed for the effect of CC12 in vivo. After treated by 10 μM CC12 for 24 h, both U118MG and U87MG cells showed tumor cell death. MTT assay results showed that the survival rates decreased when the CC12 concentrations or the treatment periods increased. Ki-67 expression and flow cytometry results indicated that the proliferation was inhibited in GBM cells, and G1 phase arrest was shown. The results of 7-AAD, Br-dUTP, and JC-1 staining all showed the apoptosis of GBM cells after CC12 treatment. Increased γH2AX, caspase-3, and poly (ADP-ribose) polymerase (PARP) levels meant the DNA damage, and increased Bcl2 family proteins after CC12 treatment indicated the intrinsic apoptotic pathway was involved in CC12 induced apoptosis. Furthermore, CC12 can induce the decrease of tumor prognostic marker DcR3. In vivo experiment results showed the effect of CC12 on tumor size reduction of CC12. In addition, the ability to cross the brain–blood barrier of CC12 was also confirmed. CC12 may have anti-tumor ability through the regulation of cell cycle and apoptosis in vitro and in vivo.

Effect of ONC201 and bortezomib on apoptosis in non-Hodgkin'™s lymphoma (NHL) xenografts.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19016-e19016 ◽  
Author(s):  
Mala Kiran Talekar ◽  
Junior Hall ◽  
Gerald B Wertheim ◽  
Daniel Martinez ◽  
Joshua E. Allen ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis ◽  
Apoptotic Cell ◽  
Xenograft Model ◽  
Combination Group ◽  
Control Group ◽  
Minimal Cell ◽  
Tumor Cell Death ◽  
Mouse Xenograft Model

e19016 Background: Our group has previously shown preclinical in vitro efficacy of novel small molecule, ONC201 across several pediatric NHL cell lines (Talekar et al, 2015) as a monoagent as well as in combination with chemotherapy agents, significantly cytarabine and bortezomib. We investigated the preclinical efficacy of ONC201 and bortezomib combination in vivo in a NHL mouse xenograft model. Methods: Burkitt’s lymphoma cell line (Ramos) transduced with lentiviral GFP was utilized to establish subcutaneous flank xenografts in 5-7 week(wk) old immunodeficient SCID mice [NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ]. All tumors were established by Day 10, detected by bioluminescent imaging and were serially imaged x1/wk. Mice were studied in 4 treatment arms (7 mice per arm) as tabulated in the table. Results: Mice in Arms 1, 2 & 3 had continued tumor growth and were humanely euthanized during Wk 3- 4 of treatment when the tumor volume reached the maximum allowable size per the approved institutional IACUC protocol. Mice in Arm 4 showed gross tumor necrosis and had to be euthanized in Wk 4. Upon treatment initiation, 2 mice in each arm were sacrificed at 48 and 72 hours respectively and tumor samples harvested for histology and IHC analysis (TRAIL and CHOP/GADD). Histological analysis revealed that the control group had predominantly viable tumor cells at both 48 & 72 H. The monoagent groups showed minimal cell death with bortezomib alone and modest cell death with ONC201 as monoagent in clustered regions. In contrast, the combination group showed: i) extensive global tumor necrosis with nuclear debris on H&E, ii) prominent TRAIL induction by IHC analysis, and, iii) significant apoptotic cell death accompanied by CHOP /GADD overexpression indicating potential ER stress. Induction of these pharmacodynamic markers in Arm 4 were evident at 48H and more prominent at the 72H. Conclusions: ONC201 effectively synergizes with bortezomib to cause apoptotic tumor cell death in pediatric NHL murine xenograft and merits further investigation. [Table: see text]

scholarly journals The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy

Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 380-393 ◽  
Author(s):  
Leigh Ellis ◽  
Michael Bots ◽  
Ralph K. Lindemann ◽  
Jessica E. Bolden ◽  
Andrea Newbold ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Response ◽  
Death Receptor ◽  
Tumor Cell Death ◽  
Antitumor Effects ◽  
Therapeutic Activities

Abstract LAQ824 and LBH589 (panobinostat) are histone deacetylase inhibitors (HDACi) developed as cancer therapeutics and we have used the Eμ-myc lymphoma model to identify the molecular events required for their antitumor effects. Induction of tumor cell death was necessary for these agents to mediate therapeutic responses in vivo and both HDACi engaged the intrinsic apoptotic cascade that did not require p53. Death receptor pathway blockade had no effect on the therapeutic activities of LAQ824 and LBH589; however, overexpression of Bcl-2 or Bcl-XL protected lymphoma cells from HDACi-induced killing and suppressed their therapeutic activities. Deletion of Apaf-1 or Caspase-9 delayed HDACi-induced lymphoma killing in vitro and in vivo, associated with suppression of many biochemical indicators of apoptosis, but did not provide long-term resistance to these agents and failed to inhibit their therapeutic activities. Eμ-myc lymphomas lacking a functional apoptosome displayed morphologic and biochemical features of autophagy after treatment with LAQ824 and LBH589, indicating that, in the absence of a complete intrinsic apoptosis pathway involving apoptosome formation, these HDACi can still mediate a therapeutic response. Our data indicate that damage to the mitochondria is the key event necessary for LAQ824 and LBH589 to mediate tumor cell death and a robust therapeutic response.

scholarly journals Weekends-Off Lenvatinib for Unresectable Hepatocellular Carcinoma Improves Therapeutic Response and Tolerability Toward Adverse Events

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1010 ◽  
Author(s):  
Hideki Iwamoto ◽  
Hiroyuki Suzuki ◽  
Shigeo Shimose ◽  
Takashi Niizeki ◽  
Masahito Nakano ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Dose Reduction ◽  
Therapeutic Response ◽  
Incidence Rates ◽  
Therapeutic Effects ◽  
Mouse Hepatoma ◽  
High Incidence Rate ◽  
Grade 3 ◽  
Hepatoma Model

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.

Sign in / Sign up

Export Citation Format

Share Document