scholarly journals Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

2016 ◽  
Vol 23 (5) ◽  
pp. 472 ◽  
Author(s):  
A. Salman ◽  
E. Simoneau ◽  
M. Hassanain ◽  
P. Chaudhury ◽  
L.M. Boucher ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combined Therapy ◽  
Evaluation Criteria ◽  
Advanced Hepatocellular Carcinoma ◽  
Response Evaluation ◽  
Initial Cohort ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Treatment Safety ◽  
90Y Radioembolization

Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc).Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed.Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar  baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months.Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit.

TACE combined with apatinib for the treatment of BCLC stage C of hepatocellular carcinoma: A restrospective controlled study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 445-445
Author(s):  
Xuefeng Kan ◽  
Bin Xiong ◽  
Yong Wang ◽  
Bin Liang ◽  
Guofeng Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Medical Records ◽  
Tumor Response ◽  
Evaluation Criteria ◽  
Controlled Study ◽  
Response Evaluation ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Response Evaluation Criteria ◽  
Time To Tumor Progression

445 Background: To access the safety and effcacy of transarterial chemoembolization (TACE) combined with apatinib (TACE-apatinib) for the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C of hepatocellular carcinoma (HCC). Methods: The medical records of 290 consecutive patients with BCLC stage C of HCC who underwent TACE-apatinib or TACE-alone from June 2015 to June 2017 were retrospectively reviewed. a-Fetoprotein (AFP) response at 4 weeks after treatment in the two groups were evaluated. Tumor response in the two groups were assessed according to modified Response Evaluation Criteria in Solid Tumors (m-RECIST) criteria. The time to tumor progression (TTP) and overall survival (OS) of patients in the two groups were evaluated respectively. Results: One hundred and ninety patients were included in the analysis; 95 patients underwent TACE-apatinib and 95 underwent TACE-alone. The baseline characteristics of patients between the two groups were comparable. The disease control rate (DCR) of tumor and AFP response in TACE-apatinib group was significantly greater than that of TACE-alone group ( P < 0.001). The median TTP was 14.0 months in the TACE-apatinib group and 3.0 months in the TACE-alone group, and the median OS was 17 months in the TACE-apatinib group and 6.0 months in the TACE-alone group. Apatinib-related adverse events of grade 3 occurred in 14 patients in TACE-apatinib group, and there was no occurrence of grade 4 adverse event. Conclusions: The adverse effects of apatinib were acceptable, and TACE-apatinib improved the outcomes for patients with BCLC stage C of HCC in comparison to TACE-alone.

Initial Experience of Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma in Clinical Practice

2021 ◽  
Vol 1 (2) ◽  
pp. 83-88
Author(s):  
TEIJI KUZUYA ◽  
NAOTO KAWABE ◽  
SENJU HASHIMOTO ◽  
RYOJI MIYAHARA ◽  
TAKUJI NAKANO ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Practice ◽  
Adverse Events ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Advanced Hepatocellular Carcinoma ◽  
Response Evaluation ◽  
Modified Recist ◽  
Grade 3

Background/Aim: The aim of this study was to investigate the outcomes of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC), including those with disease refractory to lenvatinib, in clinical practice. Patients and Methods: Of 34 patients treated with atezolizumab plus bevacizumab, a total of 23, including 16 with lenvatinib failure, were enrolled in this retrospective study. The adverse events, changes in liver function and antitumor responses at 6 weeks after starting therapy were evaluated. Results: The incidence of grade 3 adverse events was low, at 13.0%. Albumin–bilirubin scores did not worsen at 3 and 6 weeks compared to baseline. The objective response rate and disease control rate at 6 weeks were 17.4% and 78.3% according to Response Evaluation Criteria in Solid Tumors (RECIST), and 30.4% and 78.3% according to modified RECIST, respectively. Conclusion: Our results suggest that atezolizumab plus bevacizumab might have potential therapeutic safety and efficacy in patients with advanced HCC, including those with disease refractory to lenvatinib. Further studies are needed to confirm the outcomes of atezolizumab plus bevacizumab after lenvatinib failure.

scholarly journals A systematic review and network meta-analysis of second-line therapy in hepatocellular carcinoma

2020 ◽  
Vol 27 (6) ◽  
Author(s):  
S. Delos Santos ◽  
S. Udayakumar ◽  
A. Nguyen ◽  
Y.J. Ko ◽  
S. Berry ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Meta Analysis ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Clinical Benefits ◽  
Baseline Characteristics ◽  
Grade 3

Background In patients with advanced hepatocellular carcinoma (hcc) following sorafenib failure, it is unclear which treatment is most efficacious, as treatments in the second-line setting have not been directly compared and no standard therapy exists. This systematic review and network meta-analysis (nma) aimed to compare the clinical benefits and toxicities of these treatments. Methods A systematic review of randomized controlled trials (rcts) was conducted to identify phase iii rcts in advanced hcc following sorafenib failure. Baseline characteristics and outcomes of placebo were examined for het­erogeneity. Primary outcomes of interest were extracted for results, including overall survival (os), progression-free survival (pfs), objective response rate (orr), grade 3/4 toxicities, and subgroups. An nma was conducted to compare both drugs through the intermediate placebo. Comparisons were expressed as hazard ratios (hrs) for os and pfs, and as risk difference (rd) for orr and toxicities. Subgroup analyses for os and pfs were also performed. Results Two rcts were identified (1280 patients) and compared through an indirect network; celestial (cabozantinib vs. placebo) and resorce (regorafenib vs. placebo). Baseline characteristics of patients in both trials were similar. Both trials also had similar placebo outcomes. Cabozantinib, compared with regorafenib, showed similar os [hazard ratio (hr): 1.21; 95% confidence interval (ci): 0.90 to 1.62], pfs (hr: 1.02; 95% ci: 0.78 to 1.34) and orr (−3.0%; 95% ci: −7.6% to 1.7%). Both treatments showed similar toxicities, but there were marginally higher risks of grade 3/4 hand–foot syndrome (5%; 95% ci: 0.1% to 9.8%), diarrhea (4.8%; 95% ci: 1.1% to 8.5%), and anorexia (4.4%; 95% ci: 0.8% to 8.0%) for cabozantinib. Subgroup results for os and pfs were consistent with overall results. Conclusions Overall, this nma determined that cabozantinib and regorafenib have similar clinical benefits and toxicities for second-line hcc.

Efficacy and safety of apatinib combined with TACE in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15504-e15504
Author(s):  
Wei Zhang ◽  
Zhiping Yan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Transcatheter Arterial Chemoembolization ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Treatment Safety ◽  
Unacceptable Toxicity ◽  
Arterial Chemoembolization

e15504 Background: Effective options for patients with advanced hepatocellular carcinoma (HCC) are urgently needed. Studies have shown that combination of sorafenib with TACE could imorove survival for the treatment of locoregional HCCs. Apatinib is a novel and highly selective inhibitor of VEGFR2 tyrosine kinase. We were aiming to explore the efficacy and safety of apatinib combined with TACE in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Methods: This was a single-center single-arm phase 2 study. The key inclusion criteria included: (1) Histologicaly and cytologicaly diagnosed as Hepatocellular carcinoma of the liver ( HCC ) and with at least one imaging examination of measurable lesions, CT or MR scan long diameter of tumor ≥ 10 mm. (2) BCLC B / C; (3) Progressed after at least twice TACE. Eligible pts received apatinib at 500 mg/day for a maximum after TACE 4-7 days, and TACE treatment was performed after 4 days of discontinuation of apatinib until unacceptable toxicity or tumor recurrence. The primary endpoint was time to progression (TTP), which was defined as the time from enrollment to disease progression. The secondary endpoint was overall survival (OS) and treatment safety. Results: From May 27, 2018 to Oct 12, 2019, 22 pts wereenrolled. 5 pts received TACE more than 5 times, and 17 pts received TACE within 4 times. For 20 evaluable pts, two pts achieved partial response (10%), and 13 patients achieved stable disease. The ORR and DCR were 10% and 75%, respectively. At the cutoff data of Nov 4, 2019, 5 pts were still on treatment. 16 recurrenced and 5 death occurred. The mTTP was 5.09 months (95% CI, 3.48-7.16), and the mOS was not reached. Treatment-related adverse events occurred in 12 pts (60%). Seven grade 3 or 4 adverse events were reported (35%), respectively wereascites (2), platelet count decrease (1), elevated ALT/AST (1), hypertension (1), proteinuria (1) and nausea (1). None of the treatment related AEs was fatal. Conclusions: Apatinib combined with TACE might be effective and tolerant in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Clinical trial information: NCT03510416.

Phase I study of safety, pharmacokinetics, and efficacy of TSU-68 plus S-1 combination in patients with advanced hepatocellular carcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 262-262 ◽  
Author(s):  
Masafumi Ikeda ◽  
Shuichiro Shiina ◽  
Kohei Nakachi ◽  
Shuichi Mitsunaga ◽  
Satoshi Shimizu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Maximum Tolerated Dose ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Treatment Dose ◽  
Pugh Class ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Treatment Safety

262 Background: Sorafenib is the standard chemotherapy for advanced hepatocellular carcinoma (HCC), but its efficacy is limited. TSU-68 is an oral anti-angiogenesis agent that blocks VEGFR-2 and PDGFR. TSU-68 and S-1 have shown favorable efficacy and safety profile for advanced HCC (Kanai et al. 2011; Furuse et al. 2010). This study investigated the safety, tolerability, pharmacokinetics (PK), and efficacy of the TSU-68 plus S-1 combination in patients (pts) with advanced HCC. We also determined the maximum tolerated dose of TSU-68 plus S-1 on the basis of the frequency of associated dose-limiting toxicity (DLT) in this population. Methods: Pts who had not received any prior systemic therapy received 400 mg/day TSU-68 orally and one of the following doses of S-1: 50 mg/m2 (level 0), 80 mg/m2 (level 1), or 100 mg/m2 (level 2). Treatment duration was 4 weeks followed by 2-week rest (A group) or 2 weeks followed by 1-week rest (B group). The starting treatment dose and duration level was 1B, followed by progression to levels 2A and 2B. Treatment safety and tolerability at each level were assessed by enrolling 6 pts according to CTCAE v3.0. Results: Eighteen pts (6 each at levels 1B, 2A, and 2B) were enrolled (age, 58-85 years; male/female, 15/3; HCV/HBV/nBnC, 12/3/4; Child-Pugh class A/B, 18/0). Two pts each at levels 1B (grade 3 gastrointestinal bleeding, grade 2 ascites) and 2A (grade 3 fatigue, grade 3 hand-foot skin reaction) showed DLTs, but no pts at level 2B showed DLTs. The common adverse events were hemoglobin decrease, hypoalbuminemia, and anorexia; these were mild in severity (grade 1-2). PK data from 12 pts at levels 1B and 2A indicated that the area under the curve (AUC) of TSU-68 and 5-FU was unlikely to be affected by TSU-68 plus S-1. Response rate, disease control rate, median time to progression, and median overall survival time were 27.8%, 61.1%, 160 days, and 391 days, respectively. Conclusions: Our findings revealed thatthe TSU-68 plus S-1 combination was well tolerated and had favorable efficacy in patients with advanced HCC, and we recommend treatment with 400 mg/day TSU-68 and 100 mg/m2 S-1 for 4 weeks followed by 2-week rest in these patients. Clinical trial information: Japic CTI-121970.

Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma

2013 ◽  
Vol 31 (13) ◽  
pp. 1631-1639 ◽  
Author(s):  
Alexis Bujold ◽  
Christine A. Massey ◽  
John J. Kim ◽  
James Brierley ◽  
Charles Cho ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stereotactic Body Radiotherapy ◽  
Dose Range ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Advanced Hepatocellular Carcinoma ◽  
Pugh Class ◽  
Prospective Trials ◽  
Grade 3

Purpose To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). Patients and Methods Two trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors). Results A total of 102 patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis. Conclusion These results provide strong rationale for studying SBRT for HCC in a randomized trial.

Sign in / Sign up

Export Citation Format

Share Document