Literature DB >> 22438097

Systemic combination therapy of intravenous continuous 5-fluorouracil and subcutaneous pegylated interferon alfa-2a for advanced hepatocellular carcinoma.

Koji Uchino1, Shuntaro Obi, Ryosuke Tateishi, Shinpei Sato, Miho Kanda, Takahisa Sato, Toru Arano, Kenichiro Enooku, Eriko Goto, Ryota Masuzaki, Hayato Nakagawa, Yoshinari Asaoka, Yuji Kondo, Noriyo Yamashiki, Tadashi Goto, Shuichiro Shiina, Masao Omata, Haruhiko Yoshida, Kazuhiko Koike.   

Abstract

BACKGROUND: In Japan, sorafenib is now the first-line therapy for individuals with advanced hepatocellular carcinoma (HCC), but no other treatment is available for such patients. The aim of this study was to assess the efficacy and safety of combination therapy with systemic continuous intravenous infusion of 5-fluorouracil (5-FU) and subcutaneous peginterferon alfa-2a, which was used before sorafenib was introduced to Japan.
METHODS: Two hundred and twenty-three HCC patients, who were not amenable to curative surgery, percutaneous ablation, or transarterial chemoembolization (TACE), and for whom intraarterial chemotherapy was not indicated because of the presence of extrahepatic metastasis or stenosis of the common hepatic artery, received peginterferon alfa-2a (90 μg subcutaneously on days 1, 8, 15, and 22) and 5-FU (500 mg/day intravenously given continuously on days 1-5 and 8-12). We assessed their response to treatment and survival, and treatment safety.
RESULTS: The response rate was 9.4 % (including six patients with complete response) and the disease-control rate was 32.7 %. The median time to progression was 2.0 months. The overall median survival time was 6.5 months (Child-Pugh class A: 9.2 months vs. Child-Pugh class B: 2.8 months). In a multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status >0, Child-Pugh class B, and the presence of macroscopic vascular invasion were independent predictors of poor prognosis. The major grade 3-4 adverse events were leucopenia (13.9 %) and thrombocytopenia (5.8 %). No treatment-related deaths occurred.
CONCLUSIONS: This combination therapy was well tolerated and showed promising efficacy. Further studies are needed to establish the usefulness of this treatment.

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Year:  2012        PMID: 22438097     DOI: 10.1007/s00535-012-0574-3

Source DB:  PubMed          Journal:  J Gastroenterol        ISSN: 0944-1174            Impact factor:   6.772


  49 in total

1.  Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches.

Authors:  Masato Sakon; Hiroaki Nagano; Keizo Dono; Shoji Nakamori; Koji Umeshita; Akira Yamada; Sumio Kawata; Yasuharu Imai; Shohei Iijima; Morito Monden
Journal:  Cancer       Date:  2002-01-15       Impact factor: 6.860

2.  Role of the Fas/FasL pathway in combination therapy with interferon-alpha and fluorouracil against hepatocellular carcinoma in vitro.

Authors:  Masato Nakamura; Hiroaki Nagano; Masato Sakon; Tameyoshi Yamamoto; Hideo Ota; Hiroshi Wada; Bazarragchaa Damdinsuren; Takehiro Noda; Shigeru Marubashi; Atsushi Miyamoto; Yutaka Takeda; Koji Umeshita; Shoji Nakamori; Keizo Dono; Morito Monden
Journal:  J Hepatol       Date:  2006-09-25       Impact factor: 25.083

3.  Augmentation of antitumor activity of 5-fluorouracil by interferon alpha is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells.

Authors:  H Eguchi; H Nagano; H Yamamoto; A Miyamoto; M Kondo; K Dono; S Nakamori; K Umeshita; M Sakon; M Monden
Journal:  Clin Cancer Res       Date:  2000-07       Impact factor: 12.531

4.  Combination of IFN-alpha and 5-fluorouracil induces apoptosis through IFN-alpha/beta receptor in human hepatocellular carcinoma cells.

Authors:  Motoi Kondo; Hiroaki Nagano; Hiroshi Wada; Bazarragchaa Damdinsuren; Hirofumi Yamamoto; Nobuaki Hiraoka; Hidetoshi Eguchi; Atsushi Miyamoto; Tameyoshi Yamamoto; Hideo Ota; Masato Nakamura; Shigeru Marubashi; Keizo Dono; Koji Umeshita; Shoji Nakamori; Masato Sakon; Morito Monden
Journal:  Clin Cancer Res       Date:  2005-02-01       Impact factor: 12.531

5.  Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis.

Authors:  Matthias Pinter; Wolfgang Sieghart; Ivo Graziadei; Wolfgang Vogel; Andreas Maieron; Robert Königsberg; Adalbert Weissmann; Gabriela Kornek; Christina Plank; Markus Peck-Radosavljevic
Journal:  Oncologist       Date:  2009-01-14

Review 6.  Systemic therapy for advanced hepatocellular carcinoma: a review.

Authors:  Anna K Nowak; Pierce K H Chow; Michael Findlay
Journal:  Eur J Cancer       Date:  2004-07       Impact factor: 9.162

7.  Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma.

Authors:  A B Benson; E Mitchell; N Abramson; B Klencke; P Ritch; J P Burnhan; C McGuirt; T Bonny; J Levin; J Hohneker
Journal:  Ann Oncol       Date:  2002-04       Impact factor: 32.976

8.  Cancer incidence and incidence rates in Japan in 2003: based on data from 13 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project.

Authors:  Tomohiro Matsuda; Tomomi Marugame; Ken-Ichi Kamo; Kota Katanoda; Wakiko Ajiki; Tomotaka Sobue
Journal:  Jpn J Clin Oncol       Date:  2009-10-01       Impact factor: 3.019

9.  Phase II study of 5-fluorouracil (5-FU) and high dose folinic acid (HDFA) in hepatocellular carcinoma.

Authors:  A Zaniboni; E Simoncini; P Marpicati; G Marini
Journal:  Br J Cancer       Date:  1988-03       Impact factor: 7.640

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  6 in total

1.  Hypoxia induces universal but differential drug resistance and impairs anticancer mechanisms of 5-fluorouracil in hepatoma cells.

Authors:  Jing-Qiu Li; Xian Wu; Lu Gan; Xiang-Liang Yang; Ze-Hong Miao
Journal:  Acta Pharmacol Sin       Date:  2017-07-10       Impact factor: 6.150

2.  Conventional oral systemic chemotherapy for postoperative hepatocellular carcinoma: A systematic review.

Authors:  Jianhong Zhong; Bangde Xiang; Liang Ma; Lequn Li
Journal:  Mol Clin Oncol       Date:  2014-07-07

Review 3.  Natural interferon-beta treatment for patients with chronic hepatitis C in Japan.

Authors:  Reina Sasaki; Tatsuo Kanda; Shingo Nakamoto; Yuki Haga; Masato Nakamura; Shin Yasui; Xia Jiang; Shuang Wu; Makoto Arai; Osamu Yokosuka
Journal:  World J Hepatol       Date:  2015-05-18

4.  Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties.

Authors:  Ngoc Bich Vu; Tam Thanh Nguyen; Long Cong-Duy Tran; Cong Dinh Do; Bac Hoang Nguyen; Ngoc Kim Phan; Phuc Van Pham
Journal:  Cytotechnology       Date:  2012-10-27       Impact factor: 2.058

5.  A phase I/II trial of capecitabine combined with peginterferon α-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma.

Authors:  Sadahisa Ogasawara; Tetsuhiro Chiba; Yoshihiko Ooka; Naoya Kanogawa; Tenyu Motoyama; Eiichiro Suzuki; Akinobu Tawada; Fumihiko Kanai; And Osamu Yokosuka
Journal:  Invest New Drugs       Date:  2014-04-16       Impact factor: 3.850

6.  The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma.

Authors:  Fei-Xiang Wu; Jie Chen; Tao Bai; Shao-Liang Zhu; Tian-Bo Yang; Lu-Nan Qi; Ling Zou; Zi-Hui Li; Jia-Zhou Ye; Le-Qun Li
Journal:  BMC Cancer       Date:  2017-09-12       Impact factor: 4.430

  6 in total

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