Investigational New Drugs

, Volume 36, Issue 2, pp 350–353 | Cite as

Gastrointestinal perforation related to lenvatinib, an anti-angiogenic inhibitor that targets multiple receptor tyrosine kinases, in a patient with metastatic thyroid cancer

  • Emi Date
  • Kunio Okamoto
  • Souichi Fumita
  • Hiroyasu Kaneda


Lenvatinib, a novel potent multikinase inhibitor, was approved for the treatment of radioiodine-refractory differentiated thyroid cancer based on results from phase III trial (SELECT study). Thyroid cancer is a diverse disease that includes anaplastic thyroid cancer (ATC), which the most aggressive form of the disease, although it accounts for <2% of all thyroid cancers. Current treatments for ATC have limited efficacy. We report the case of a woman with recurrent well-differentiated papillary carcinoma of the thyroid that had transformed into ATC who developed a perforation of the small intestine secondary to a marked effect of lenvatinib. She received lenvatinib (24 mg once a day) at only two doses during two weeks due to pleurodesis with talc for malignant pleural effusion. Eventually, she developed peritonitis due to the perforation and died of sepsis. However, an autopsy revealed marked efficacy of lenvatinib for ATC at a metastatic site in the small intestine despite limited exposure to the drug. Here, we report on our experience with lenvatinib treatment and gastrointestinal perforation concerning anti-angiogenic therapy.


Lenvatinib Anaplastic thyroid cancer Anti-angiogenic inhibitor Gastrointestinal perforation Tyrosine kinase inhibitor Case report 


Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.


  1. 1.
    Perri F, Lorenzo GD, Scarpati GD et al (2011) Anaplastic thyroid carcinoma: a comprehensive review of current and future therapeutic options. World J Clin Oncol 2:150–157CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sipos JA, Shah MH (2010) Thyroid cancer: emerging role for targeted therapies. Ther Adv Med Oncol 2:3–16CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Denaro N, Nigro CL, Russi EG, Merlano MC (2013) The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer. Onco Targets Ther 9:1231–1241CrossRefPubMedGoogle Scholar
  4. 4.
    Schlumberger M, Tahara M, Wirth LJ et al (2015) Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372:621–630CrossRefPubMedGoogle Scholar
  5. 5.
    Tahara M, Kiyota N, Yamazaki T, Chayahara N, Nakano K, Inagaki L, Toda K, Enokida T, Minami H, Imamura Y, Sasaki T, Suzuki T, Fujino K, Dutcus CE, Takahashi S (2017) Lenvatinib for Anaplastic Thyroid Cancer. Front Oncol 7:25CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Klein M, Picard E, Vignaud JM et al (1999) Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma. J Endocrinol 161:41–49CrossRefPubMedGoogle Scholar
  7. 7.
    Tohyama O, Matsui J, Kodama K et al (2014) Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models. J Thyroid Res 2014:638747CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hapani S, Chu D, Wu S (2009) Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol 10:559–568CrossRefPubMedGoogle Scholar
  9. 9.
    Qi WX, Sun YJ, Tang LN, Shen Z, Yao Y (2014) Risk of gastrointestinal perforation in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis. (2014). Crit Rev Oncol Hematol 89:394–403CrossRefPubMedGoogle Scholar
  10. 10.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl J Med 350:2335–2342CrossRefPubMedGoogle Scholar
  11. 11.
    Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, Mazier MA, Canon JL, Georgoulias V, Peeters M, Bridgewater J, Cunningham D (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20:1842–1847CrossRefPubMedGoogle Scholar
  12. 12.
    Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14:1860–1869CrossRefPubMedGoogle Scholar
  13. 13.
    Badgwell BD, Camp ER, Feig B, Wolff RA, Eng C, Ellis LM, Cormier JN (2008) Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol 19:577–582CrossRefPubMedGoogle Scholar
  14. 14.
    Parikh AA, Ellis LM (2008) Targeted therapies and surgical issues in gastrointestinal cancers. Targ. Oncologia 3:119–125Google Scholar
  15. 15.
    Walraven M, Witteveen PO, Lolkema MP, van Hillegersberg R, Voest EE, Verheul HM (2011) Antiangiogenic tyrosine kinase inhibition related gastrointestinal perforations: a case report and literature review. Angiogenesis 14:135–141CrossRefPubMedGoogle Scholar
  16. 16.
    Park SG, Chung CH, Park CY (2011) Colon perforation during sorafenib therapy for advanced hepatocelluar carcinoma. A case report. Tumori 97:794–799CrossRefPubMedGoogle Scholar
  17. 17.
    Inoue T, Kinoshita H, Komai Y, Kawabata T, Kawa G, Uemura Y, Matsuda T (2012) Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma. World J Surg Oncol 10:167CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Medical OncologyKishiwada City HospitalOsakaJapan
  2. 2.Kagawa Prefectural Central HospitalKagawaJapan

Personalised recommendations