scholarly journals PHARMACOLOGICAL THERAPY OF HEPATOCELLULAR CANCER PRACTICAL ISSUES AND SOLUTIONS

2017 ◽  
pp. 11-23
Author(s):  
V. V. Breder ◽  
K. K. Laktionov ◽  
M. I. Davydov
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Hepatocellular Cancer ◽  
Pharmacological Therapy ◽  
Second Line Therapy ◽  
Clinical Issue ◽  
Pharmaceutical Therapy ◽  
Hepatocellular Carcinomas ◽  
Strategic Goal

Pharmaceutical therapy of hepatocellular carcinoma represents a major clinical issue of debate in modern oncology. Until now, Sorafenib remains the only option for the management of locally advanced and metastatic hepatocellular carcinomas, which increases the overall survival of patients. In the absence of alternative treatment, the oncologist understanding of the place, time, the strategic goal and tactical objectives of the pharmaceutical therapy of hepatocellular carcinoma at different stages of cancer is of great importance. The article considers the practical aspects of the Sorafenib therapy of hepatocellular cancer in various clinical situations, and proposes algorithms of accompanying therapy for the underlying liver pathology. It presents the results of Regorafenib therapy, a new multi-kinase inhibitor, which significantly increases survival in the second line therapy of sorafenib-resistant hepatocellular  carcinoma. The options  of  pharmaceutical therapy for hepatocellular  carcinoma using cytotoxic and molecular-directed medicines, prospects of modern immunotherapy are discussed.

Selection of Patients with Hepatocellular Carcinoma for Sorafenib

2009 ◽  
Vol 7 (4) ◽  
pp. 397-403 ◽  
Author(s):  
Ghassan K. Abou-Alfa
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Phase Iii ◽  
Vegf Receptor ◽  
Raf Kinase ◽  
Advanced Cirrhosis ◽  
Phase Iii Studies ◽  
Selection Of Patients ◽  
Selection Of

Sorafenib, a multitargeted anti-VEGF receptor and raf kinase inhibitor, was recently approved by the FDA for treating unresectable hepatocellular carcinoma (HCC) based on 2 randomized phase III studies. In addition, a phase II study evaluating sorafenib in patients with HCC and Child-Pugh A and B and a phase I study evaluating sorafenib in patients with organ dysfunction have provided insight about the safety and efficacy of sorafenib in patients with HCC and more advanced cirrhosis, and any difference in outcome based on etiology of HCC. The lack of objective responses observed in the sorafenib arm in the SHARP study also raises practical issues about how to assess response or efficacy of the therapy and thus how long a patient should receive sorafenib. This article addresses these questions on the use of sorafenib in HCC, both in the locally advanced and metastatic settings, in addition to the potential future applications and uses of sorafenib.

scholarly journals Current State of Liver-Directed Therapies and Combinatory Approaches with Systemic Therapy in Hepatocellular Carcinoma (HCC)

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1085 ◽  
Author(s):  
Pedro Viveiros ◽  
Ahsun Riaz ◽  
Robert J. Lewandowski ◽  
Devalingam Mahalingam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Therapy ◽  
Immune Cell ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Tumor Biology ◽  
Arterial Embolization ◽  
Intermediate Stage ◽  
Current Evidence ◽  
Ablative Techniques

The increasing set of liver-directed therapies (LDT) have become an integral part of hepatocellular carcinoma (HCC) treatment. These range from percutaneous ablative techniques to arterial embolization, and varied radiotherapy strategies. They are now used for local disease control, symptom palliation, and bold curative strategies. The big challenge in the face of these innovative and sometimes overlapping technologies is to identify the best opportunity of use. In real practice, many patients may take benefit from LDT used as a bridge to curative treatment such as resection and liver transplantation. Varying trans-arterial embolization strategies are used, and comparison between established and developing technologies is scarce. Also, radioembolization utilizing yttrium-90 (Y-90) for locally advanced or intermediate-stage HCC needs further evidence of clinical efficacy. There is increasing interest on LDT-led changes in tumor biology that could have implications in systemic therapy efficacy. Foremost, additional to its apoptotic and necrotic properties, LDT could warrant changes in vascular endothelial growth factor (VEGF) expression and release. However, trans-arterial chemoembolization (TACE) used alongside tyrosine-kinase inhibitor (TKI) sorafenib has had its efficacy contested. Most recently, interest in associating Y-90 and TKI has emerged. Furthermore, LDT-led differences in tumor immune microenvironment and immune cell infiltration could be an opportunity to enhance immunotherapy efficacy for HCC patients. Early attempts to coordinate LDT and immunotherapy are being made. We here review LDT techniques exposing current evidence to understand its extant reach and future applications alongside systemic therapy development for HCC.

scholarly journals Optimizing Survival and the Changing Landscape of Targeted Therapy for Intermediate and Advanced Hepatocellular Carcinoma: A Systematic Review

2020 ◽  
Author(s):  
Howard Lim ◽  
Ravi Ramjeesingh ◽  
Dave Liu ◽  
Vincent C Tam ◽  
Jennifer J Knox ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Kinase Inhibitor ◽  
Hepatocellular Cancer ◽  
Phase Iii ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Patient Reported ◽  
Phase Iii Trials

Abstract Background Systemic therapy for hepatocellular carcinoma (HCC) consisting of the tyrosine kinase inhibitor sorafenib has remained unchanged for over a decade, although results from phase III targeted therapy trials have recently emerged. This review considers available phase III evidence on the use and sequencing of targeted therapy for intermediate and advanced non-locoregional therapy (LRT) eligible HCC and discusses implications for clinical practice Methods Published and presented literature on phase III data reporting on targeted therapy for advanced HCC that was not eligible for loco-regional therapies was identified using the key search terms “hepatocellular cancer” AND “advanced” AND “targeted therapy” AND “phase III” OR respective aliases (PRISMA). Results Ten phase III trials assessed targeted therapy first-line and eight following sorafenib. In the first-line, atezolizumab plus bevacizumab statistically significantly improved overall survival (OS) and patient-reported outcomes (PROs) compared with sorafenib, while lenvatinib demonstrated non-inferior OS. Following progression on sorafenib, statistically significant OS improvements over placebo were seen for cabozantinib and regorafenib in unselected patients and for ramucirumab in those with baseline α-fetoprotein≥400 ng/mL. Based on improved OS and PROs, atezolizumab plus bevacizumab appears to be a preferred first-line treatment option for intermediate or advanced non-LRT eligible HCC. Phase III data informing sequencing of later lines of treatment is lacking. Therefore, sequencing principles are proposed that can be used to guide treatment selection. Conclusions Ongoing trials will continue to inform optimal therapy. Multiple targeted therapies have improved OS in intermediate or advanced non-LRT eligible HCC, although optimal sequencing is an area of ongoing investigation.

scholarly journals En bloc transdiaphragmatic lung resection for locally advanced hepatocellular carcinoma: a case report

2020 ◽  
Vol 2020 (6) ◽  
Author(s):  
Kit-fai Lee ◽  
Randolph H L Wong ◽  
Howard H W Leung ◽  
Eugene Y J Lo ◽  
Charing C N Chong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Locally Advanced ◽  
Left Lung ◽  
Lower Lobe ◽  
Uneventful Recovery ◽  
Advanced Hepatocellular Carcinoma ◽  
Right Hepatectomy ◽  
En Bloc ◽  
Liver Recurrence ◽  
Lung Base

Abstract A 56-year-old man presented with an 11-cm hepatocellular carcinoma (HCC) at segment 7 of liver. To induce left liver hypertrophy, a sequential transarterial chemoembolization (TACE) and portal vein embolization before right hepatectomy were adopted. However, the tumor further increased in size despite TACE and invaded through the diaphragm to the right lung base. Anterior approach right hepatectomy with en bloc wedge resection of the involved right lower lobe of lung by endovascular staplers via transdiaphragmatic approach was performed. The diaphragmatic defect was closed with Goretex mesh. Patient made an uneventful recovery. Pathology confirmed a 12.5 cm poorly differentiated HCC invading through diaphragm to lung. During follow-up, patient developed a 6 cm recurrence at left lung base 17 months after surgery for which he received sorafenib therapy. However, the lung mass further increased in size with new liver recurrence at segment 3 despite treatment. He succumbed 2 years and 3 months after surgery.

scholarly journals Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

2021 ◽  
Vol 13 ◽  
pp. 175883592110311
Author(s):  
Chiun Hsu ◽  
Lorenza Rimassa ◽  
Hui-Chuan Sun ◽  
Arndt Vogel ◽  
Ahmed O. Kaseb
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Healthcare Providers ◽  
Safety Data ◽  
Standard Of Care ◽  
Antiangiogenic Agents ◽  
Efficacy And Safety ◽  
First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

scholarly journals Avelumab in Combination with Axitinib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma: Results from the Phase 1b VEGF Liver 100 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Masatoshi Kudo ◽  
Kenta Motomura ◽  
Yoshiyuki Wada ◽  
Yoshitaka Inaba ◽  
Yasunari Sakamoto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Recist 1.1 ◽  
Phase 1B ◽  
Grade 3

<b><i>Introduction:</i></b> Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. <b><i>Methods:</i></b> Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. <b><i>Results:</i></b> Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (<i>n</i> = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (<i>n</i> = 5 [22.7%]), and decreased appetite (<i>n</i> = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. <b><i>Conclusion:</i></b> Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.

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