A prospective clinical trial on sorafenib treatment of hepatocellular carcinoma before liver transplantation.
Adult
Aged
Antineoplastic Agents
/ administration & dosage
Blood Flow Velocity
Carcinoma, Hepatocellular
/ drug therapy
Drug Tolerance
Female
Follow-Up Studies
Humans
Liver Neoplasms
/ drug therapy
Liver Transplantation
Male
Middle Aged
Neoadjuvant Therapy
Pilot Projects
Prospective Studies
Quality of Life
Response Evaluation Criteria in Solid Tumors
Sorafenib
/ administration & dosage
Tomography, X-Ray Computed
Feasibility
Hepatocellular carcinoma
Liver cancer
Liver transplantation
Neoadjuvant
Perfusion CT
Sorafenib
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
11 Jun 2019
11 Jun 2019
Historique:
received:
05
11
2018
accepted:
27
05
2019
entrez:
13
6
2019
pubmed:
13
6
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma. Twelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012-August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo. Baseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired. This study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study. EudraCT number: 2010-024306-36 (date 2011-04-07).
Sections du résumé
BACKGROUND
BACKGROUND
Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma.
METHODS
METHODS
Twelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012-August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo.
RESULTS
RESULTS
Baseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired.
CONCLUSIONS
CONCLUSIONS
This study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study.
TRIAL REGISTRATION
BACKGROUND
EudraCT number: 2010-024306-36 (date 2011-04-07).
Identifiants
pubmed: 31185950
doi: 10.1186/s12885-019-5760-8
pii: 10.1186/s12885-019-5760-8
pmc: PMC6560824
doi:
Substances chimiques
Antineoplastic Agents
0
Sorafenib
9ZOQ3TZI87
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
568Subventions
Organisme : Bayer HealthCare
ID : 15559/2010
Références
Hepatology. 2001 Jun;33(6):1394-403
pubmed: 11391528
Cancer Res. 2006 Dec 15;66(24):11851-8
pubmed: 17178882
Radiology. 2007 Jun;243(3):736-43
pubmed: 17517931
Oncologist. 2008 Feb;13(2):120-5
pubmed: 18305056
N Engl J Med. 2008 Jul 24;359(4):378-90
pubmed: 18650514
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Ann Surg. 2009 Aug;250(2):187-96
pubmed: 19638912
Hepatology. 2010 Jan;51(1):165-73
pubmed: 19877181
Lancet Oncol. 2010 Apr;11(4):373-82
pubmed: 20171141
Semin Liver Dis. 2010 Feb;30(1):52-60
pubmed: 20175033
J Gastrointest Cancer. 2010 Dec;41(4):217-20
pubmed: 20443078
Med Oncol. 2011 Dec;28(4):1044-7
pubmed: 20635167
Transplant Proc. 2010 Dec;42(10):4582-4
pubmed: 21168742
Cancer. 2012 Jan 1;118(1):147-56
pubmed: 21713764
Transpl Int. 2011 Oct;24(10):991-8
pubmed: 21777298
Eur J Cancer. 2012 Jul;48(10):1452-65
pubmed: 22240282
Eur Radiol. 2012 Jul;22(7):1430-41
pubmed: 22367468
Eur J Cancer. 2012 Mar;48(5):599-641
pubmed: 22424278
Clin Transplant. 2012 Sep-Oct;26(5):764-74
pubmed: 22432589
Radiology. 2012 Nov;265(2):448-56
pubmed: 22996748
Eur J Radiol. 2013 May;82(5):e205-11
pubmed: 23273822
Liver Int. 2013 Apr;33(4):605-15
pubmed: 23305331
PLoS One. 2013;8(1):e53960
pubmed: 23349774
Dig Liver Dis. 2013 Sep;45(9):776-81
pubmed: 23578581
Transpl Int. 2013 Jul;26(7):734-9
pubmed: 23701126
Br J Radiol. 2014 Mar;87(1035):20130695
pubmed: 24452058
J Hepatol. 2014 Aug;61(2):309-17
pubmed: 24681342
BMC Cancer. 2015 May 11;15:392
pubmed: 25957784
Ann Surg. 2015 Sep;262(3):536-45; discussion 543-5
pubmed: 26258323
Lancet Oncol. 2015 Oct;16(13):1344-54
pubmed: 26361969
Ann Transl Med. 2015 Nov;3(19):285
pubmed: 26697445
Radiology. 2016 Nov;281(2):454-464
pubmed: 27171020
Transplantation. 2017 Sep;101(9):2071-2078
pubmed: 28353492
J Am Coll Surg. 2017 Jul;225(1):28-40
pubmed: 28400300
Hepatology. 2018 Jan;67(1):381-400
pubmed: 28859222
Eur J Radiol. 2018 Jan;98:41-49
pubmed: 29279169
Transpl Int. 2018 May;31(5):531-539
pubmed: 29380442
World J Gastroenterol. 2018 Aug 21;24(31):3469-3471
pubmed: 30131653
Ann Surg Treat Res. 2018 Sep;95(3):152-160
pubmed: 30182022