Relationship between adverse events associated with lenvatinib treatment for thyroid cancer and patient prognosis

Iwasaki,Hiroyuki; Toda,Soji; Murayama,Daisuke; Kato,Shin; Matsui,Ai

doi:10.3892/mco.2020.2190

Relationship between adverse events associated with lenvatinib treatment for thyroid cancer and patient prognosis

Authors:
- Hiroyuki Iwasaki
- Soji Toda
- Daisuke Murayama
- Shin Kato
- Ai Matsui
View Affiliations

Affiliations: Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa 241‑8515, Japan
Published online on: December 16, 2020 https://doi.org/10.3892/mco.2020.2190
Article Number: 28
Copyright: © Iwasaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tyrosine kinase inhibitors (TKIs) were first approved for treating radioactive iodine‑refractory differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC) 5 years ago. Among them, lenvatinib has a high response rate and has become the first‑line drug for treating thyroid cancer. Although it has a high response rate, it is also characterized by a high frequency of adverse events (AEs). AEs previously reported in a phase II study occurred after the practical application of TKI therapy. However, the type and frequency of AEs that occurred were significantly different. The present study investigated the type and frequency of AEs in the real‑world setting and examined their relationship with prognosis. Between June 2015 and May 2020, 111 patients (79 patients with DTC and 32 patients with ATC) were treated with lenvatinib. An investigation of lenvatinib AEs, including fatal events, revealed that fistula formation or severe tumor regrowth after the discontinuation of treatment was an AE associated with poor prognosis. In total, 11 patients with ATC (34.4%) and 7 patients with DTC (8.9%) developed skin fistula. The mortality rate among these patients was 38.9% (7/18), including three deaths caused by major bleeding and four deaths attributable to mediastinitis or pneumonia. In the DTC group, irreversible regrowth occurred in all 7 patients who required drug withdrawal because of AEs, and all patients died. Conversely, overall survival was longer among patients with DTC and hand‑foot syndrome (HFS). Therefore, the present study illustrated that although lenvatinib therapy can result in severe AEs requiring dose reduction or treatment discontinuation, the HFS appearance portends a good prognosis in patients treated with lenvatinib.

View Figures

View References

1	Seib CD and Sosa JA: Evolving understanding of the epidemiology of thyroid cancer. Endocrinol Metab Clin North Am. 48:23–35. 2019.PubMed/NCBI View Article : Google Scholar
2	Olson E, Wintheiser G, Wolfe KM, Droessler J and Silberstein PT: Epidemiology of thyroid cancer: A review of the National Cancer Database, 2000-2013. Cureus. 11(e4127)2019.PubMed/NCBI View Article : Google Scholar
3	Melosky B, Leighl NB, Rothenstein J, Sangha R, Stewart D and Papp K: Management of EGFR TKI-induced dermatologic adverse events. Curr Oncol. 22:123–132. 2015.PubMed/NCBI View Article : Google Scholar
4	Eskazan AE and Ozmen D: Tyrosine kinase inhibitor (TKI) therapy for newly-diagnosed patients with chronic myeloid leukemia: Focusing on TKI discontinuation due to adverse events-is better always good? Expert Rev Hematol. 10:583–586. 2017.PubMed/NCBI View Article : Google Scholar
5	Haugen BR: 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: What is new and what has changed? Cancer. 123:372–381. 2017.PubMed/NCBI View Article : Google Scholar
6	Iwasaki H, Yamazaki H, Takasaki H, Suganuma N, Sakai R, Nakayama H, Hatori S, Toda S and Masudo K: Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors. Oncol Lett. 17:5292–5300. 2019.PubMed/NCBI View Article : Google Scholar
7	Kamba T and McDonald DM: Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 96:1788–1795. 2007.PubMed/NCBI View Article : Google Scholar
8	Sonpavde G, Bellmunt J, Schutz F and Choueiri TK: The double edged sword of bleeding and clotting from VEGF inhibition in renal cancer patients. Curr Oncol Rep. 14:295–306. 2012.PubMed/NCBI View Article : Google Scholar
9	Machiels JP, Henry S, Zanetta S, Kaminsky MC, Michoux N, Rommel D, Schmitz S, Bompas E, Dillies AF, Faivre S, et al: Phase II study of sunitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: GORTEC 2006-01. J Clin Oncol. 28:21–28. 2010.PubMed/NCBI View Article : Google Scholar
10	Mancuso MR, Davis R, Norberg SM, O'Brien S, Sennino B, Nakahara T, Yao VJ, Inai T, Brooks P, Freimark B, et al: Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 116:2610–2621. 2006.PubMed/NCBI View Article : Google Scholar
11	Liu L, Wang E, Li L, Chen D, Peng K, Wang M and Han G: As clinical markers, hand-foot-skin reaction and diarrhea can predict better outcomes for hepatocellular carcinoma patients receiving transarterial chemoembolization plus sorafenib. Can J Gastroenterol Hepatol. 2019(2576349)2019.PubMed/NCBI View Article : Google Scholar
12	Falcone G, Arrigoni C, Dellafiore F, Gallucci F, Milani V, Boveri S, Ausili D and Caruso R: A systematic review and meta-analysis on the association between hand-foot syndrome (HFS) and cancer chemotherapy efficacy. Clin Ter. 170:e388–e395. 2019.PubMed/NCBI View Article : Google Scholar
13	Kobayashi K, Kawakami K, Yokokawa T, Aoyama T, Suzuki K, Wakatsuki T, Suenaga M, Sato H, Sugiyama E, Yamaguchi K and Hama T: Association of hand-foot skin reaction with regorafenib efficacy in the treatment of metastatic colorectal cancer. Oncology. 96:200–206. 2019.PubMed/NCBI View Article : Google Scholar
14	Iwasaki H, Yamazaki H, Takasaki H, Suganuma N, Sakai R, Nakayama H, Toda S and Masudo K: Renal dysfunction in patients with radioactive iodine-refractory thyroid cancer treated with tyrosine kinase inhibitors: A retrospective study. Medicine (Baltimore). 98(e17588)2019.PubMed/NCBI View Article : Google Scholar
15	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009.PubMed/NCBI View Article : Google Scholar
16	Iwasaki H, Yamazaki H, Takasaki H, Suganuma N, Nakayama H, Toda S and Masudo K: Lenvatinib as a novel treatment for anaplastic thyroid cancer: A retrospective study. Oncol Lett. 16:7271–7277. 2018.PubMed/NCBI View Article : Google Scholar
17	Iwasaki H, Toda S, Suganuma N, Murayama D, Nakayama H and Masudo K: Lenvatinib vs. palliative therapy for stage IVC anaplastic thyroid cancer. Mol Clin Oncol. 12:138–143. 2020.PubMed/NCBI View Article : Google Scholar
18	Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, et al: Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 372:621–630. 2015.PubMed/NCBI View Article : Google Scholar
19	Locati LD, Piovesan A, Durante C, Bregni M, Castagna MG, Zovato S, Giusti M, Ibrahim T, Puxeddu E, Fedele G, et al: Real-world efficacy and safety of lenvatinib: Data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy. Eur J Cancer. 118:35–40. 2019.PubMed/NCBI View Article : Google Scholar
20	Hui EP, Ma BBY, King AD, Mo F, Chan SL, Kam MKM, Loong HH, Ahuja AT, Zee BCY and Chan ATC: Hemorrhagic complications in a phase II study of sunitinib in patients of nasopharyngeal carcinoma who has previously received high-dose radiation. Ann Oncol. 22:1280–1287. 2011.PubMed/NCBI View Article : Google Scholar
21	Blevins DP, Dadu R, Hu M, Baik C, Balachandran D, Ross W, Gunn B and Cabanillas ME: Aerodigestive fistula formation as a rare side effect of antiangiogenic tyrosine kinase inhibitor therapy for thyroid cancer. Thyroid. 24:918–922. 2014.PubMed/NCBI View Article : Google Scholar
22	Katsura Y, Takeda Y, Ohmura Y, Sakamoto T, Kawai K, Inatome J, Murakami K, Naito A, Kagawa Y, Masuzawa T, et al: Experience of treatment with lenvatinib in patients with advanced HCC-A in a single institution. Gan To Kagaku Ryoho. 46:2101–2103. 2019.PubMed/NCBI(In Japanese).
23	Yada M, Masumoto A, Motomura K, Tajiri H, Morita Y, Suzuki H, Senju T and Koyanagi T: Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma. World J Gastroenterol. 20:12581–12587. 2014.PubMed/NCBI View Article : Google Scholar