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.

Concomitant chemoradiation using gemcitabine in locally advanced hepatocellular carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15611-e15611
Author(s):  
A. I. Masood ◽  
A. A. Javed ◽  
A. Mateen ◽  
S. A. Gurchani
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Treatment Response Evaluation ◽  
Standard Management ◽  
Concomitant Chemoradiation ◽  
Grade 3

e15611 Background: Hepatocellular carcinoma (HCC) is among the most common malignancies in Pakistan. There is currently no standard management for advanced HCC. Non-surgical modalities have demonstrated minimal improvements in survival. The aim of present study is to assess response rate and toxicity of concomitant gemcitabine and external radiation therapy (ERT) in locally advanced HCC. Methods: Thirty three biopsy proven advanced HCC patients having Okuda stage I and II disease were enrolled. 70 mg/m2 gemcitabine was given once weekly for three weeks during ERT. Partial liver ERT was delivered with 60Co upto 30 gray (Gy), 1.8 Gy/fraction and five fractions in a week. Tumor response was assessed by computed tomography (CT) eight weeks after completion of treatment. Response Evaluation Criteria in Solid Tumors (RECIST) was used to assess complete and partial response (CR, PR); progressive and stable disease (PD, SD). Hematological [neutropenia and thrombocytopenia], gastrointestinal (vomiting and diarrhea) and liver [encephalopathy, bilirubin, alanine and aspartate transferases (ALT and AST), and alkaline phosphatase (ALP)] toxicities were assessed weekly during treatment and then fortnightly upto 2 months according to Common Toxicity Criteria for Adverse Events version (3.0). Primary end point was to assess response rate at eight weeks after completion of treatment and Grade 3 or 4 toxicity during this period. Results: 28/33 patients were evaluable. No CR was seen. PR, SD and PD (%) were seen in 36, 39 and 25 of patients respectively. No grade 3 or 4 neutropenia was observed. 7/28 (25%) of patients developed grade 3 thrombocytopenia during treatment and needed a delay of one week for gemcitabine administration. Grade 3/4 toxicity (%) related to vomiting, diarrhea, encephalopathy, bilirubin, ALT, AST and ALP was seen in 18, 29, 21, 18, 14, 29 and 32 of the patients. Conclusions: The study showed that concomitant chemoradiation using 70mg/m2 gemcitabine is a feasible option with acceptable toxicity in locally advanced HCC. A larger study will be appropriate to define its definite role. No significant financial relationships to disclose.

Randomized Controlled Trial of Tamoxifen in Advanced Hepatocellular Carcinoma

2005 ◽  
Vol 23 (19) ◽  
pp. 4338-4346 ◽  
Author(s):  
Jean-Claude Barbare ◽  
Olivier Bouché ◽  
Franck Bonnetain ◽  
Jean-Luc Raoul ◽  
Philippe Rougier ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Performance Status ◽  
Univariate Analysis ◽  
Local Treatment ◽  
Cox Proportional Hazards Model ◽  
Tamoxifen Treatment ◽  
Control Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Pugh Class

Purpose Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC. Patients and Methods A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 μmol/L were not eligible. Results Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages. Conclusion In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.

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.

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.

A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 354-354
Author(s):  
Eiichiro Suzuki ◽  
Shuichi Kaneko ◽  
Takuji Okusaka ◽  
Masafumi Ikeda ◽  
Kensei Yamaguchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Performance Status ◽  
Objective Response ◽  
Japanese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Class A ◽  
Pugh Class ◽  
Grade 3

354 Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.

scholarly journals Advanced Hepatocellular Carcinoma With Hepatic Arterioportal Shunts: Combination Treatment of Transarterial Chemoembolization With Apatinib

2020 ◽  
Vol 7 ◽  
Author(s):  
Tao Sun ◽  
Yanqiao Ren ◽  
Xuefeng Kan ◽  
Lei Chen ◽  
Weihua Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Tumor Progression ◽  
Transarterial Chemoembolization ◽  
Protective Factor ◽  
Evaluation Criteria ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Grade 3

Object: This study aimed to compare the efficacy and safety of transarterial chemoembolization (TACE) combining with apatinib (TACE-apatinib) and TACE-alone for patients with advanced hepatocellular carcinoma (HCC) with hepatic arterioportal shunts (APS).Materials and Methods: This retrospective study evaluated the medical records of patients with advanced HCC with APS who underwent TACE-apatinib or TACE-alone from June 2015 to January 2019. The occlusion of the shunt was performed during the TACE procedure. The time to tumor progression (TTP) and overall survival (OS) of study patients were evaluated. The modified Response Evaluation Criteria in solid tumors (mRECIST) was used to evaluate the treatment response. The apatinib-related adverse events were recorded.Results: Fifty-eight patients were included in this study. Twenty-seven patients underwent the treatment of TACE-apatinib, and 31 received TACE-alone treatment. The median overall survival (OS) and median time of tumor progression (TTP) in the TACE-apatinib group were significantly longer than those of the TACE-alone group (OS: 12.0 vs. 9.0 months, P = 0.000; TTP: 9.0 vs. 5.0 months, P = 0.041). Multivariate analysis revealed that TACE-apatinib was a protective factor for OS, and there was no independent risk factor for TTP. In the TACE-apatinib group, the grade 3 apatinib-related adverse events occurred in four patients.Conclusion: TACE-apatinib was an efficacious and safe treatment for patients with advanced HCC with APS, and apatinib improved the efficacy of TACE in the treatment of these patients.

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.

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.

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