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Article

Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors

  • Authors:
    • Philipp Ivanyi
    • Hendrik Eggers
    • Mareike Hornig
    • Bernd Kasper
    • Klaus Heissner
    • Hans-Georg Kopp
    • Martha Kirstein
    • Arnold Ganser
    • Viktor Grünwald
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D‑30625 Hannover, Germany, Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, University of Heidelberg, D‑68167 Mannheim, Germany, Department of Oncology, Hematology, Clinical Immunology, Rheumatology and Pneumology, University Hospital and Faculty of Medicine Tübingen, D‑72076 Tübingen, Germany, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, D‑30625 Hannover, Germany
  • Article Number: 72
    |
    Published online on: September 21, 2020
       https://doi.org/10.3892/mco.2020.2143
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Abstract

Regorafenib is a multi‑target tyrosine kinase inhibitor that has been approved for the treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors (GIST). Severe hepatobiliary toxicity has been reported in patients with colorectal cancer treated with regorafenib, but not in those with GIST. Therefore, the aim of the present study was to investigate the incidence and clinical course of regorafenib‑associated hepatic toxicity (HT) in patients with GIST in a real‑world setting. Patients with metastatic GIST treated with regorafenib between September 2012 and May 2014 at three German tertiary care centers were followed up until August 2017. Patient records were retrospectively analyzed and descriptive statistics were employed. HT was defined as alterations in the serum values of aspartate aminotransferase, alanine aminotransferase, γ‑glutamyltransferase, alkaline phosphatase and bilirubin (according to the Common Terminology Criteria for Adverse Events, version 4.0), and/or corresponding clinical signs. The time to clinical progression and the overall survival were calculated by Kaplan‑Meier curves. Overall, 21 patients were treated with regorafenib and 5 (23.5%) of those heavily pretreated patients suffered from severe HT during regorafenib treatment. In 4 (80%) of these cases, regorafenib treatment was continued, optimizing individual treatment benefit. Clinical monitoring and adequate therapy management are crucial for ensuring continuation of regorafenib treatment in order to achieve an optimal clinical outcome.
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1 

Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schütz G, Thierauch KH and Zopf D: Regorafenib (BAY 73-4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 129:245–255. 2011.PubMed/NCBI View Article : Google Scholar

2 

Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, et al: Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 381:295–302. 2013.PubMed/NCBI View Article : Google Scholar

3 

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 381:303–312. 2013.PubMed/NCBI View Article : Google Scholar

4 

Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, et al: Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 389:56–66. 2017.PubMed/NCBI View Article : Google Scholar

5 

Roderburg C, Özdirik B, Wree A, Demir M and Tacke F: Systemic treatment of hepatocellular carcinoma: From sorafenib to combination therapies. Hepat Oncol. 7(HEP20)2020.PubMed/NCBI View Article : Google Scholar

6 

Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, et al: Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial. J Clin Oncol. 28:1061–1068. 2010.PubMed/NCBI View Article : Google Scholar

7 

Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, et al: Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 47:2117–2127. 2011.PubMed/NCBI View Article : Google Scholar

8 

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, et al: Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 27:3584–3590. 2009.PubMed/NCBI View Article : Google Scholar

9 

Iacovelli R, Palazzo A, Procopio G, Santoni M, Trenta P, De Benedetto A, Mezi S and Cortesi E: Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy. Br J Clin Pharmacol. 77:929–938. 2014.PubMed/NCBI View Article : Google Scholar

10 

World Medical Association. World medical association declaration of helsinki: Ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013.PubMed/NCBI View Article : Google Scholar

11 

Cancer Therapy Evaluation Programm D NCI, NIH, DHHS: Common terminology criteria for adverse events v4.0 (CTCAE), 2009.

12 

Komatsu Y, Doi T, Sawaki A, Kanda T, Yamada Y, Kuss I, Demetri GD and Nishida T: Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: A subgroup analysis evaluating Japanese patients in the phase III GRID trial. Int J Clin Oncol. 20:905–912. 2015.PubMed/NCBI View Article : Google Scholar

13 

Kollàr A, Maruzzo M, Messiou C, Cartwright E, Miah A, Martin-Liberal J, Thway K, McGrath E, Dunlop A, Khabra K, et al: Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: A report of the UK managed access program. Clin Sarcoma Res. 4(17)2014.PubMed/NCBI View Article : Google Scholar

14 

Chamberlain F, Farag S, Williams-Sharkey C, Collingwood C, Chen L, Mansukhani S, Engelmann B, Al-Muderis O, Chauhan D, Thway K, et al: Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre. Clin Sarcoma Res. 10(1)2020.PubMed/NCBI View Article : Google Scholar

15 

Schvartsman G, Wagner MJ, Amini B, Zobniw CM, Trinh VA, Barbo AG, Lin HY, Wang WL, Conley AP, Ravi V, et al: Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients. Sci Rep. 7(9519)2017.PubMed/NCBI View Article : Google Scholar

16 

Xu CF, Reck BH, Xue Z, Huang L, Baker KL, Chen M, Chen EP, Ellens HE, Mooser VE, Cardon LR, et al: Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 102:1371–1377. 2010.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Ivanyi P, Eggers H, Hornig M, Kasper B, Heissner K, Kopp H, Kirstein M, Ganser A and Grünwald V: Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors. Mol Clin Oncol 13: 72, 2020.
APA
Ivanyi, P., Eggers, H., Hornig, M., Kasper, B., Heissner, K., Kopp, H. ... Grünwald, V. (2020). Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors. Molecular and Clinical Oncology, 13, 72. https://doi.org/10.3892/mco.2020.2143
MLA
Ivanyi, P., Eggers, H., Hornig, M., Kasper, B., Heissner, K., Kopp, H., Kirstein, M., Ganser, A., Grünwald, V."Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors". Molecular and Clinical Oncology 13.6 (2020): 72.
Chicago
Ivanyi, P., Eggers, H., Hornig, M., Kasper, B., Heissner, K., Kopp, H., Kirstein, M., Ganser, A., Grünwald, V."Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors". Molecular and Clinical Oncology 13, no. 6 (2020): 72. https://doi.org/10.3892/mco.2020.2143
Copy and paste a formatted citation
x
Spandidos Publications style
Ivanyi P, Eggers H, Hornig M, Kasper B, Heissner K, Kopp H, Kirstein M, Ganser A and Grünwald V: Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors. Mol Clin Oncol 13: 72, 2020.
APA
Ivanyi, P., Eggers, H., Hornig, M., Kasper, B., Heissner, K., Kopp, H. ... Grünwald, V. (2020). Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors. Molecular and Clinical Oncology, 13, 72. https://doi.org/10.3892/mco.2020.2143
MLA
Ivanyi, P., Eggers, H., Hornig, M., Kasper, B., Heissner, K., Kopp, H., Kirstein, M., Ganser, A., Grünwald, V."Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors". Molecular and Clinical Oncology 13.6 (2020): 72.
Chicago
Ivanyi, P., Eggers, H., Hornig, M., Kasper, B., Heissner, K., Kopp, H., Kirstein, M., Ganser, A., Grünwald, V."Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors". Molecular and Clinical Oncology 13, no. 6 (2020): 72. https://doi.org/10.3892/mco.2020.2143
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