J Liver Cancer.  2021 Sep;21(2):194-198. 10.17998/jlc.2021.09.20.

A case report of a patient presented with skin ulcer after treatment of lenvatinib

• Cha S
• Kim DW
• Choe JW
• Kim TH
• Kim SY
• Hyun JJ
• Jung SW
• Koo JS
• Jung YK
• Yim HJ

• KMID: 2520908
• DOI: http://doi.org/10.17998/jlc.2021.09.20

Abstract

A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.

Keyword

Lenvatinib mesylate; Skin ulcer; Hepatocellular carcinoma; Adverse drug event; Protein kinase inhibitor

Figure

• 

  Figure 1 The primovist-enhanced magnetic resonance imaging of the hepatocellular carcinoma at initial diagnosis: (A) early enhancement of the tumor in the T1 arterial enhanced phase (red arrow), (B) early washout in venous phase (red arrow), and (C) a tumor thrombosis in the main portal vein in portal phase (blue arrow).

• 

  Figure 2 Photograph of the cutaneous lesion. (A) The buttock lesion at initial presentation after 2 months of Lenvatinib. Ulceration is observed in the perineal area, extending from behind the scrotum to the anus. The patient complained of perineal pain, and the skin lesion was associated with bloody discharge, full-thickness skin loss and tissue necrosis, corresponding to Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV. (B) The cutaneous lesion improved dramatically after 10 days after discontinuation of lenvatinib, surgical procedure and antibiotic treatment.

Reference

References

1. Dipasquale A, Marinello A, Santoro A. A comparison of lenvatinib versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma: selection criteria to guide physician’s choice in a new therapeutic scenario. J Hepatocell Carcinoma. 2021; 8:241–251.

2. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Len vatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 noninferiority trial. Lancet. 2018; 391:1163–1173.

3. Yamashita T, Kudo M, Ikeda K, Izumi N, Tateishi R, Ikeda M, et al. REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. J Gastroenterol. 2020; 55:113–122.

4. Liu Z, Li X, He X, Xu Y, Wang X. Complete response to the combination of Lenvatinib and Pembrolizumab in an advanced hepatocellular carcinoma patient: a case report. BMC Cancer. 2019; 19:1062.

5. European Medicines Agency. Lenvima 2015 [Internet]. Amsterdam (NL): European Medicines Agency;[cited 2015 Mar 26]. Available from: https://www.ema.europa.eu/en/documents/assessment-report/lenvima-epar-public-assessment-report_en.pdf .

6. Dohmen K. Severe ulcerative skin lesions due to lenvatinib. Clin Gastroenterol Hepatol. 2020; 18:e113.

7. Kitamura M, Hayashi T, Suzuki C, Hirano S, Tateya I, Kishimoto Y, et al. Successful recovery from a subclavicular ulcer caused by lenvatinib for thyroid cancer: a case report. World J Surg Oncol. 2017; 15:24.

8. US Department of Health and Human Services. Common Terminology Criteria Adverse Events (CTCAE) Version 4.0. 2009. [Internet]. Washington, DC (USA): U.S. Department of Health and Human Services;[cited 2009 May 28]. Available from: https://evs.nci.nih.gov/ftp1/CT-CAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf .

9. Yamamoto Y, Matsui J, Matsushima T, Obaishi H, Miyazaki K, Nakamura K, et al. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell. 2014; 6:18.

10. Schlumberger M, Jarzab B, Cabanillas ME, Robinson B, Pacini F, Ball DW, et al. A phase II trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer. Clin Cancer Res. 2016; 22:44–53.

11. Tahara M, Kiyota N, Yamazaki T, Chayahara N, Nakano K, Inagaki L, et al. Lenvatinib for anaplastic thyroid cancer. Front Oncol. 2017; 7:25.

12. Fleeman N, Houten R, Chaplin M, Beale S, Boland A, Dundar Y, et al. A systematic review of lenvatinib and sorafenib for treating progressive, locally advanced or metastatic, differentiated thyroid cancer after treatment with radioactive iodine. BMC Cancer. 2019; 19:1209.

13. Suyama K, Iwase H. Lenvatinib: a promising molecular targeted agent for multiple cancers. Cancer Control. 2018; 25:1073274818789361.

14. Takahashi S, Kiyota N, Tahara M. Optimal use of lenvatinib in the treatment of advanced thyroid cancer. Cancers Head Neck. 2017; 2:7.

15. Kim SY, Kim SM, Chang H, Kim BW, Lee YS, Chang HS, et al. Safety of tyrosine kinase inhibitors in patients with differentiated thyroid cancer: real-world use of lenvatinib and sorafenib in Korea. Front Endocrinol. 2019; 10:384.