Effectiveness and Safety of Sorafenib in the Treatment of Unresectable and Advanced Intrahepatic Cholangiocarcinoma: a Pilot Study

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Oct 27

PMID 27783997

Citations 15

Authors

Xiangji Luo

Weidong Jia

Zhiyong Huang

Xiangcheng Li

Baocai Xing

Xiaoqing Jiang

Jun Li

Anfeng Si

Tian Yang

Chunfang Gao

Wan Yee Lau

Feng Shen

Affiliations

Soon will be listed here.

Abstract

Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of sorafenib combined with best supportive care (BSC) in these patients. We enrolled 44 patients with unresectable and advanced ICC who were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12, and the secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Our results showed that the DCR was 15.9%, the median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). AEs of grades 1 and 2 events occurred in 75% of patients, and AE of grade 4 (severe) was observed in 1 patient. Therefore, sorafenib in combination with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC.

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References

Valle J, Wasan H, Palmer D, Cunningham D, Anthoney A, Maraveyas A . Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010; 362(14):1273-81. DOI: 10.1056/NEJMoa0908721. View

Wilhelm S, Carter C, Tang L, Wilkie D, McNabola A, Rong H . BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004; 64(19):7099-109. DOI: 10.1158/0008-5472.CAN-04-1443. View

Moehler M, Maderer A, Schimanski C, Kanzler S, Denzer U, Kolligs F . Gemcitabine plus sorafenib versus gemcitabine alone in advanced biliary tract cancer: a double-blind placebo-controlled multicentre phase II AIO study with biomarker and serum programme. Eur J Cancer. 2014; 50(18):3125-35. DOI: 10.1016/j.ejca.2014.09.013. View

Sugiyama H, Onuki K, Ishige K, Baba N, Ueda T, Matsuda S . Potent in vitro and in vivo antitumor activity of sorafenib against human intrahepatic cholangiocarcinoma cells. J Gastroenterol. 2011; 46(6):779-89. DOI: 10.1007/s00535-011-0380-3. View

Maithel S, Clark Gamblin T, Kamel I, Corona-Villalobos C, Thomas M, Pawlik T . Multidisciplinary approaches to intrahepatic cholangiocarcinoma. Cancer. 2013; 119(22):3929-42. DOI: 10.1002/cncr.28312. View

DeOliveira M, Cunningham S, Cameron J, Kamangar F, Winter J, Lillemoe K . Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007; 245(5):755-62. PMC: 1877058. DOI: 10.1097/01.sla.0000251366.62632.d3. View

Weber S, Ribero D, OReilly E, Kokudo N, Miyazaki M, Pawlik T . Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015; 17(8):669-80. PMC: 4527852. DOI: 10.1111/hpb.12441. View

Valle J, Furuse J, Jitlal M, Beare S, Mizuno N, Wasan H . Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol. 2013; 25(2):391-8. DOI: 10.1093/annonc/mdt540. View

Scheuermann U, Kaths J, Heise M, Pitton M, Weinmann A, Hoppe-Lotichius M . Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma--a single-center experience. Eur J Surg Oncol. 2013; 39(6):593-600. DOI: 10.1016/j.ejso.2013.03.010. View

10.

Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A . Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010; 103(4):469-74. PMC: 2939781. DOI: 10.1038/sj.bjc.6605779. View

11.

Park J, Kim M, Kim K, Park D, Moon S, Song T . Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study. Gut Liver. 2010; 3(4):298-305. PMC: 2852727. DOI: 10.5009/gnl.2009.3.4.298. View

12.

Okusaka T, Ishii H, Funakoshi A, Yamao K, Ohkawa S, Saito S . Phase II study of single-agent gemcitabine in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol. 2005; 57(5):647-53. DOI: 10.1007/s00280-005-0095-3. View

13.

Bengala C, Bertolini F, Malavasi N, Boni C, Aitini E, Dealis C . Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial. Br J Cancer. 2009; 102(1):68-72. PMC: 2813746. DOI: 10.1038/sj.bjc.6605458. View

14.

Okabayashi T, Yamamoto J, Kosuge T, Shimada K, Yamasaki S, Takayama T . A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables. Cancer. 2001; 92(9):2374-83. DOI: 10.1002/1097-0142(20011101)92:9<2374::aid-cncr1585>3.0.co;2-l. View

15.

LaRocca R, Hicks M, Mull L, Foreman B . Effective palliation of advanced cholangiocarcinoma with sorafenib: a two-patient case report. J Gastrointest Cancer. 2008; 38(2-4):154-6. DOI: 10.1007/s12029-008-9028-9. View

16.

Burger I, Hong K, Schulick R, Georgiades C, Thuluvath P, Choti M . Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: initial experience in a single institution. J Vasc Interv Radiol. 2005; 16(3):353-61. DOI: 10.1097/01.RVI.0000143768.60751.78. View

17.

Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T, Ojima H . Surgical outcomes of the mass-forming plus periductal infiltrating types of intrahepatic cholangiocarcinoma: a comparative study with the typical mass-forming type of intrahepatic cholangiocarcinoma. World J Surg. 2007; 31(10):2016-22. DOI: 10.1007/s00268-007-9194-0. View

18.

Lee J, Capanu M, OReilly E, Ma J, Chou J, Shia J . A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas. Br J Cancer. 2013; 109(4):915-9. PMC: 3749586. DOI: 10.1038/bjc.2013.432. View

19.

El-Khoueiry A, Rankin C, Ben-Josef E, Lenz H, Gold P, Hamilton R . SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma. Invest New Drugs. 2011; 30(4):1646-51. PMC: 3490705. DOI: 10.1007/s10637-011-9719-0. View

20.

Penz M, Kornek G, Raderer M, Ulrich-Pur H, Fiebiger W, Lenauer A . Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol. 2001; 12(2):183-6. DOI: 10.1023/a:1008352123009. View