PURPOSE: To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double-blind phase II trial. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early- or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P < .05 indicated a significant difference. RESULTS:Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years ± 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients receivedbevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. CONCLUSION: No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE.
RCT Entities:
PURPOSE: To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double-blind phase II trial. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early- or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P < .05 indicated a significant difference. RESULTS: Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years ± 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients received bevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. CONCLUSION: No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE.
Authors: Susanne Smolka; Julius Chapiro; Wilfred Manzano; John Treilhard; Eric Reiner; Yanhong Deng; Yan Zhao; Bernd Hamm; James S Duncan; Bernhard Gebauer; MingDe Lin; Jean-François Geschwind Journal: Clin Imaging Date: 2017-06-07 Impact factor: 1.605
Authors: Choi-Fong Cho; Lihai Yu; Tienabe K Nsiama; Alisha N Kadam; Arun Raturi; Sourabh Shukla; Giulio A Amadei; Nicole F Steinmetz; Leonard G Luyt; John D Lewis Journal: Nanoscale Date: 2017-08-24 Impact factor: 7.790
Authors: Shuren Li; Markus Peck-Radosavljevic; Philipp Ubl; Wolfgang Wadsak; Markus Mitterhauser; Eva Rainer; Matthias Pinter; Hao Wang; Christian Nanoff; Klaus Kaczirek; Alexander Haug; Marcus Hacker Journal: Eur J Nucl Med Mol Imaging Date: 2017-05-29 Impact factor: 9.236