scholarly journals Mistletoe Extract Viscum Fraxini-2 for Treatment of Advanced Hepatocellular Carcinoma: A Case Series

2021 ◽  
pp. 224-231
Author(s):  
Richard T. Lee ◽  
Peiying Yang ◽  
Asrar Alahmadi ◽  
Jennifer McQuade ◽  
Eric Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Time ◽  
Injection Site Reaction ◽  
Case Series ◽  
Advanced Hepatocellular Carcinoma ◽  
Site Reaction ◽  
Advanced Hcc ◽  
Mistletoe Extract ◽  
Sorafenib Therapy ◽  
Mistletoe Extracts

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of death from cancer worldwide, and for advanced HCC the prognosis is poor. Preliminary studies indicate mistletoe extracts may have anticancer activity for HCC. Methods: A prospective observational case series of advanced HCC patients that chose to take a mistletoe extract called viscum fraxini-2 (VF-2) alone for treatment. Time on treatment, imaging, and laboratory values were collected for descriptive analyses. Results: A total of 12 patients with advanced HCC enrolled onto the protocol, and 10 patients had data available for evaluation. The majority were male (10/12) with a median age of 64 (SD 11). Most patients had received sorafenib therapy (9/12) and had varying Child-Pugh classes (A-4, B-6, C-2). Treatment with VF-2 ranged from 1 to 36 weeks with a mean of 12.3 weeks (SD 12). Six patients received 8 weeks of treatment, and 3 patients received 12 or more weeks of treatment. For patients that received at least 4 weeks of treatment, the average AFP value stabilized during the first 4 weeks of treatment. Two patients experienced an AFP decrease of >30%, approximately 37 and 40% decreases at the nadir. One patient had stable disease of 9 months. Major side effects were fever, fatigue, rash, and local injection site reaction of swelling, redness, and tenderness. Conclusion: This case series of advanced HCC indicates that mistletoe extract VF-2 may have potential biological activity against HCC for selected patients. Research is needed to identify the active compound and predictive markers of response.

scholarly journals Combination of Sorafenib, Camrelizumab, Transcatheter Arterial Chemoembolization, and Stereotactic Body Radiation Therapy as a Novel Downstaging Strategy in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Case Series Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yun Huang ◽  
Zeyu Zhang ◽  
Weijun Liao ◽  
Kuan Hu ◽  
Zhiming Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Adverse Events ◽  
Tumor Thrombus ◽  
Stereotactic Body Radiation Therapy ◽  
Transcatheter Arterial Chemoembolization ◽  
Case Series ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Arterial Chemoembolization

Background and AimAlthough the treatment effect and availability of therapeutic options for advanced hepatocellular carcinoma (HCC) are limited, the downstaging strategy may improve patient prognosis. This study aimed to investigate the potential of combination therapy as a downstaging strategy for treating advanced HCC with portal vein tumor thrombus (PVTT).MethodsThis retrospective case series included patients having advanced HCC with PVTT, who received the combination therapy of sorafenib, camrelizumab, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) from January 2019 to December 2019 in Xiangya Hospital, Central South University. The downstaging rate, treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated.ResultsOf the 13 patients, HCC downstaging was achieved in 4 (33.3%) patients who later received hepatectomy. The overall response rate was 41.7%, and the disease control rate was 50.0%. The median PFS time was 15.7 months, with a 1-year PFS rate of 58.3%, whereas the median OS was not reached after 1 year (1-year OS, 83.3%). No severe adverse events or grade 3–4 adverse effect was observed in 12 of the 13 enrolled patients; therapy had to be discontinued in only one patient due to adverse events, who was excluded from the study. The most common adverse effect was fever (n = 4, 33.3%), followed by skin reaction (n = 3, 25%).ConclusionA combination therapy comprising sorafenib, camrelizumab, TACE, and SBRT is an effective downstaging strategy for advanced HCC with PVTT and is associated with few adverse events.

Systemic targeted and immunotherapy for advanced hepatocellular carcinoma

2020 ◽  
Author(s):  
Robert J Cersosimo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Effects ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Advanced Hepatocellular Carcinoma ◽  
Targeted Agents ◽  
Phase 3 ◽  
Advanced Hcc ◽  
Sorafenib Therapy

Abstract Purpose The activity of targeted agents and immunotherapy in the management of advanced hepatocellular carcinoma (HCC) is reviewed. Summary The first drug approved by the Food and Drug Administration for advanced HCC, sorafenib, was approved in 2007. Regorafenib, the second drug, was approved 10 years later. Six additional drugs have been approved since. Targeted agents and checkpoint inhibitors are the only agents approved for systemic therapy of advanced HCC. Sorafenib and lenvatinib are approved as first-line agents, with regorafenib, cabozantinib, ramucirumab, nivolumab (used alone or with ipilimumab), and pembrolizumab approved for patients who have received prior sorafenib therapy. Most patients in phase 3 studies had Child-Pugh class A cirrhosis, and data on the use of these agents in patients with more advanced hepatic dysfunction are limited. All of the targeted agents improve survival in patients with advanced disease. Median overall survival durations of up to 12.3 and 13.6 months were reported with use of sorafenib and lenvatinib, respectively, in phase 3 trials. Overall survival durations of 10.6, 10.2, and 9.2 months have been achieved with use of regorafenib, cabozantinib, and ramucirumab as second-line therapy after sorafenib. A median overall survival of 13.2 months was reported in 1 cohort of a dose-expansion study of nivolumab in which all patients received prior sorafenib therapy. Median survival durations of 12.9 months and 13.9 months were reported with use of pembrolizumab in patients with a history of sorafenib therapy. The most common adverse effects associated with targeted agents are dermatological effects, diarrhea, fatigue, and hypertension. Immune-mediated adverse effects are associated with checkpoint inhibitors. Conclusion Targeted agents and checkpoint inhibitors are the standard of therapy for patients who need systemic therapy for advanced HCC.

scholarly journals Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

2021 ◽  
Vol 9 (2) ◽  
pp. e001945 ◽  
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gerry Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Cho Wing Li ◽  
Roland Leung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Acquired Resistance ◽  
Survival Rates ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Advanced Hcc

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

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

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

2017 ◽  
Vol 36 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Christian Labenz ◽  
Vera Prenosil ◽  
Sandra Koch ◽  
Yvonne Huber ◽  
Jens U. Marquardt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The Metabolic Syndrome ◽  
The Impact

Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma by placing a temporary catheter via the subclavian route

2007 ◽  
Vol 48 (7) ◽  
pp. 734-740 ◽  
Author(s):  
Huei-Lung Liang ◽  
Jer-Shyung Huang ◽  
Yi-Huei Lin ◽  
Kwok-Hung Lai ◽  
Chien-Fang Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Hepatic Arterial Infusion ◽  
Catheter Placement ◽  
Hepatic Arterial Infusion Chemotherapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Arterial Infusion ◽  
Arterial Infusion Chemotherapy ◽  
Advanced Hcc ◽  
Infusion Chemotherapy

Background: A permanent reservoir implantation is considered mandatory for hepatic arterial infusion chemotherapy (HAIC) of hepatocellular carcinoma (HCC). Since treatment sessions of HAIC may be limited for these end-staged patients, a simple alternative technique for this treatment is desirable. Purpose: To evaluate the feasibility of placing a temporary catheter for HAIC in advanced HCC patients. Material and Methods: 25 advanced HCC patients underwent HAIC with drugs delivered from a temporary catheter which was placed percutaneously by puncturing the left subclavian artery under ultrasound guidance. A course of chemotherapy consisted of five consecutive daily infusions of 5-fluorouracil, cisplatin, mitomycin C, and leucovorin. The catheter was removed on the 6th day. Therapy was repeated every 4–6 weeks with maximal number of courses of up to six. The total courses of HAIC in each patient, the catheter-placed-related complications, tumor response rate, and median survival of the patients were registered. Results: A total of 77 courses of HAIC were performed with 100% technical success of catheter placement (1–6 courses in each patient, average 3.1 courses). The overall response rate was 20%, with complete response in two patients and partial response in three patients. Eleven (55%) of the 20 non-responders died within 5 months (mean HAIC, two courses). None of the patients experienced complications such as catheter occlusion, hepatic arterial thrombosis, cerebral infarction, or local infection. Conclusion: With fewer catheter-related complications, HAIC by temporary catheter placement via subclavian puncture could be a treatment option.

scholarly journals Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Mei ◽  
Yu-Hao Tang ◽  
Wei Wei ◽  
Ming Shi ◽  
Lie Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Arterial Infusion ◽  
Progression Free Survival ◽  
Good Survival ◽  
Hepatic Artery Infusion ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Infusion Chemotherapy ◽  
Hepatic Artery Infusion Chemotherapy ◽  
Cell Death Protein

BackgroundLenvatinib combined with programmed cell death protein-1 (PD-1) inhibitors has resulted in good survival outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) has also attracted attention due to its high response rates and favorable survival for advanced HCC patients. The present study aimed to compare the efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib (HPL) and PD-1 inhibitors plus lenvatinib (PL) in patients with advanced HCC.MethodsBetween July 2018 and December 2019, patients diagnosed with advanced HCC who initially received HPL or PL treatment were reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.ResultsIn total, 70 patients met the criteria and were included in the present study, and they were divided into the HPL group (n = 45) and PL group (n = 25). The overall response rate (40.0 vs. 16.0%, respectively; p = 0.038) and disease control rate (77.6 vs. 44.0%, respectively; p &lt; 0.001) were higher in the HPL group than in the PL group. The median overall survival was 15.9 months in the HPL group and 8.6 months in the PL group (p = 0.0015; HR = 0.6; 95% CI 0.43–0.83). The median progression-free survival was 8.8 months in the HPL group and 5.4 months in the PL group (p = 0.0320; HR = 0.74; 95% CI 0.55–0.98).ConclusionCompared to PL, HPL was associated with a significantly better treatment response and survival benefits for patients with advanced HCC.

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