TACE plus sorafenib for the treatment of advanced hepatocellular carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15178-e15178
Author(s):  
Vijay Sukhdeo Palwe ◽  
Rajnish Vasant Nagarkar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Good Method ◽  
Advanced Hepatocellular Carcinoma ◽  
Multikinase Inhibitor ◽  
Unresectable Hepatocellular Carcinoma ◽  
Ecog Ps

e15178 Background: Hepatocellular carcinoma (HCC) is considered to be a hypervascular tumor. Therefore, Trans Arterial Chemo Embolization (TACE) and inhibition of angiogenesis appear rational treatment strategies for those patients who have localised disease not amenable to surgical resection. TACE causes increased hypoxia leading to an up regulation in hypoxia inducible factor-1α (HIF-1α), which in turn up regulates vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor, and increases tumor angiogenesis. The present study investigated for the combination of TACE and Sorafenib, a multikinase inhibitor with anti-angiogenic activities approved for the treatment of HCC. Methods: Patients included histologically confirmed, unresectable hepatocellular carcinoma beyond Milan criteria, no extrahepatic spread, Child Pugh score ≤8, ECOG PS 0-2, platelets >100K/µl, and bilirubin <2.5 mg/dl. We present our experience with 42 patients of HCC treated with Trans Arterial Chemo Embolisation (TACE) with Cisplatin, Lipodol and PVA of which 14 pts received TACE along with Sorafenib. Results: Between May 2007 to Jan 2013, 42 patients were enrolled. Patients received a mean of 1.45 TACE interventions (range 1-4). The longest survival was 53 months after 1stTACE and median overall survival was 443 days. Grade 3 and 4 toxicities were noted in 18% and 7% of patients. Conclusions: TACE is a very good method for palliation of unresectable hepatocellular carcinoma (HCC) with improved survival and quality of life.The combination of TACE with sorafenib is tolerable for most patients and associated with a promising rate of radiographic response and OS.

scholarly journals Perforation of the Small Intestine after Introduction of Lenvatinib in a Patient with Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 14 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Naomi Suzuki ◽  
Kazuto Tajiri ◽  
Yuka Futsukaichi ◽  
Shinichi Tanaka ◽  
Aiko Murayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Intestine ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Vascular Endothelial ◽  
First Line ◽  
Endothelial Growth Factor ◽  
Line Standard

Lenvatinib is a first-line standard treatment for advanced hepatocellular carcinoma (HCC) with better anti-tumor effects than sorafenib, as shown by greater inhibition of the kinases of fibroblast growth factor receptor and vascular endothelial growth factor (VEGF) receptor. This report describes a patient with advanced HCC who experienced perforation of the small intestine 1 month after starting the treatment with lenvatinib. This patient likely had partial necrosis of a metastasis to the small intestine before starting lenvatinib treatment, with subsequent ischemic changes leading to perforation of the small intestine. Although metastasis of HCC to the small intestine is rare, patients with these metastases should be regarded as being at risk for perforation during lenvatinib treatment.

Phase II study of cetuximab in patients with unresectable or metastatic hepatocellular carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14096-14096 ◽  
Author(s):  
A. X. Zhu ◽  
L. Blaszkowsky ◽  
P. C. Enzinger ◽  
P. Bhargava ◽  
D. P. Ryan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Egfr Expression ◽  
Epidermal Growth

14096 Background: Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis with no established systemic treatment regimen. Epidermal growth factor receptor/human epidermal growth factor receptor 1 (EGFR/HER1) and ligand expression is frequently seen in HCC. Recent studies suggest that erlotinib, an EGFR/HER1 tyrosine kinase inhibitor, may have benefit in stabilizing HCC. We performed a phase II study with cetuximab, a chimeric monoclonal antibody that binds selectively to EGFR, in advanced HCC. Methods: Eligibility criteria include unresectable or metastatic measurable HCC, up to two prior systemic regimens, performance status ≤ 2, CLIP score ≤ 3, and adequate organ functions. The initial dose of cetuximab is 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. Each cycle is defined as 6 consecutive weekly treatments. EGFR expression was assayed by immunohistochemistry and trough serum concentrations of cetuximab were determined during the first cycle. The primary endpoint of the study was progression free survival (PFS). Results: The planned 30 patients have been enrolled: median age = 58 (33–82), M/F = 23/7, ECOG 0/1/2 = 16/12/2, CLIP 0/1/2/3=2/9/14/5. No responses were seen. Five patients had stable disease. The median number of cycles on study per patient was 1 (range, 1–3). 16 patients developed progressive disease following one cycle of treatment. Only one patient remains on study. The median PFS and OS were 41 days (95% CI, 36 to 79) and 157 days (95% CI, 112 to not available), respectively. The treatment was generally well tolerated. No treatment related deaths occurred. Treatment related grade 1–2 toxicities included rash (83%), fatigue (47%), hypomagnesemia (27%), nausea (20%), anemia (13%), diarrhea (13%), anorexia (13%), and elevation of SGOT/SGPT (10%). Grade 3 SGOT, hypomagnesemia, and fever without neutropenia were seen in one patient (3%) each. Conclusions: Cetuximab has no activity in HCC in this phase II study. It can be safely given with tolerable toxicity profiles in HCC patients. Updated information on toxicity, efficacy, EGFR expression and pharmacokinetics will be presented at the meeting. Supported by Bristol-Myers Squibb. [Table: see text]

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Median Overall Survival ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

scholarly journals Axitinib in combination with radiotherapy for advanced hepatocellular carcinoma: a phase I clinical trial

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kai-Lin Yang ◽  
Mau-Shin Chi ◽  
Hui-Ling Ko ◽  
Yi-Ying Huang ◽  
Su-Chen Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase I ◽  
Response Rate ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Normal Liver ◽  
Maximum Tolerated Dose ◽  
Outcome Analysis ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

Abstract Background To investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1–3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC). Methods This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local–regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS). Results Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months. Conclusions Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort. Trial registration ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461

Molecular Mechanism and Prediction of Sorafenib Chemoresistance in Human Hepatocellular Carcinoma

2015 ◽  
Vol 33 (6) ◽  
pp. 771-779 ◽  
Author(s):  
Naoshi Nishida ◽  
Masayuki Kitano ◽  
Toshiharu Sakurai ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Kinase Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Growth Factor Receptor ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, and prognosis remains unsatisfactory when the disease is diagnosed at an advanced stage. Many molecular targeted agents are being developed for the treatment of advanced HCC; however, the only promising drug to have been developed is sorafenib, which acts as a multi-kinase inhibitor. Unfortunately, a subgroup of HCC is resistant to sorafenib, and the majority of these HCC patients show disease progression even after an initial satisfactory response. To date, a number of studies have examined the underlying mechanisms involved in the response to sorafenib, and trials have been performed to overcome the acquisition of drug resistance. The anti-tumor activity of sorafenib is largely attributed to the blockade of the signals from growth factors, such as vascular endothelial growth factor receptor and platelet-derived growth factor receptor, and the downstream RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade. The activation of an escape pathway from RAF/MEK/ERK possibly results in chemoresistance. In addition, there are several features of HCCs indicating sorafenib resistance, such as epithelial-mesenchymal transition and positive stem cell markers. Here, we review the recent reports and focus on the mechanism and prediction of chemoresistance to sorafenib in HCC.

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