Literature DB >> 24737402

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

Sadahisa Ogasawara1, Tetsuhiro Chiba, Yoshihiko Ooka, Naoya Kanogawa, Tenyu Motoyama, Eiichiro Suzuki, Akinobu Tawada, Fumihiko Kanai, And Osamu Yokosuka.   

Abstract

BACKGROUND: Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II).
METHODS: Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m(2)∙day)] and peginterferon α-2a (μg/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively.
RESULTS: A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events.
CONCLUSION: Capecitabine at 2000 mg/(m(2)∙day) combined with peginterferon α-2a (90 μg/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.

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Year:  2014        PMID: 24737402     DOI: 10.1007/s10637-014-0097-2

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  23 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.  Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study.

Authors:  Jordi Bruix; Won-Young Tak; Antonio Gasbarrini; Armando Santoro; Massimo Colombo; Ho-Yeong Lim; Vincenzo Mazzaferro; Reiner Wiest; María Reig; Andrea Wagner; Luigi Bolondi
Journal:  Eur J Cancer       Date:  2013-06-25       Impact factor: 9.162

3.  Efficacy of combination chemotherapy with capecitabine plus cisplatin in patients with unresectable hepatocellular carcinoma.

Authors:  Ju Hyun Shim; Joong-Won Park; Byung Ho Nam; Woo Jin Lee; Chang-Min Kim
Journal:  Cancer Chemother Pharmacol       Date:  2008-04-25       Impact factor: 3.333

4.  Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study.

Authors:  Josep M Llovet; Thomas Decaens; Jean-Luc Raoul; Eveline Boucher; Masatoshi Kudo; Charissa Chang; Yoon-Koo Kang; Eric Assenat; Ho-Yeong Lim; Valerie Boige; Philippe Mathurin; Laetitia Fartoux; Deng-Yn Lin; Jordi Bruix; Ronnie T Poon; Morris Sherman; Jean-Frédéric Blanc; Richard S Finn; Won-Young Tak; Yee Chao; Rana Ezzeddine; David Liu; Ian Walters; Joong-Won Park
Journal:  J Clin Oncol       Date:  2013-08-26       Impact factor: 44.544

5.  PTK787/ZK222584 combined with interferon alpha and 5-fluorouracil synergistically inhibits VEGF signaling pathway in hepatocellular carcinoma.

Authors:  Yoshiteru Katsura; Hiroshi Wada; Masahiro Murakami; Hirofumi Akita; Naoki Hama; Koichi Kawamoto; Shogo Kobayashi; Shigeru Marubashi; Hidetoshi Eguchi; Masahiro Tanemura; Koji Umeshita; Yuichiro Doki; Masaki Mori; Hiroaki Nagano
Journal:  Ann Surg Oncol       Date:  2013-03-19       Impact factor: 5.344

6.  Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease.

Authors:  Thomas Yau; Hilda Wong; Pierre Chan; T J Yao; R Pang; T T Cheung; S T Fan; Ronnie T Poon
Journal:  Invest New Drugs       Date:  2012-03-09       Impact factor: 3.850

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

Authors:  Koji Uchino; 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
Journal:  J Gastroenterol       Date:  2012-03-22       Impact factor: 6.772

8.  Management of hepatocellular carcinoma: an update.

Authors:  Jordi Bruix; Morris Sherman
Journal:  Hepatology       Date:  2011-03       Impact factor: 17.425

9.  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.

Authors:  Scott M Wilhelm; Christopher Carter; Liya Tang; Dean Wilkie; Angela McNabola; Hong Rong; Charles Chen; Xiaomei Zhang; Patrick Vincent; Mark McHugh; Yichen Cao; Jaleel Shujath; Susan Gawlak; Deepa Eveleigh; Bruce Rowley; Li Liu; Lila Adnane; Mark Lynch; Daniel Auclair; Ian Taylor; Rich Gedrich; Andrei Voznesensky; Bernd Riedl; Leonard E Post; Gideon Bollag; Pamela A Trail
Journal:  Cancer Res       Date:  2004-10-01       Impact factor: 13.312

10.  Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial.

Authors:  V Boige; J-L Raoul; J-P Pignon; O Bouché; J-F Blanc; L Dahan; J-L Jouve; N Dupouy; M Ducreux
Journal:  Br J Cancer       Date:  2007-09-18       Impact factor: 7.640

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  2 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.  Apatinib treatment may improve survival outcomes of patients with hepatitis B virus-related sorafenib-resistant hepatocellular carcinoma.

Authors:  Yingqiang Zhang; Guihua Huang; Hongfei Miao; Ze Song; Xiaoying Zhang; Wenzhe Fan; Yu Wang; Jiaping Li; Yong Chen
Journal:  Ther Adv Med Oncol       Date:  2020-07-23       Impact factor: 8.168

  2 in total

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