Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Oct 19;12(1):303.
doi: 10.1186/s13256-018-1849-y.

Alectinib (Alecensa)-induced reversible grade IV nephrotoxicity: a case report and review of the literature

P Ramachandran  1 , R Morcus  2 , M Tahir  3 , I Onukogu  2 , B Spinowitz  3 , Jen C Wang  4
Affiliations
Review

Alectinib (Alecensa)-induced reversible grade IV nephrotoxicity: a case report and review of the literature

P Ramachandran et al. J Med Case Rep. .

Abstract

Background: Lung cancer is among the top causes of cancer-related mortality in men and is the second most common cancer after breast cancer in women. There are approximately 234,030 new cases of lung cancer and 154,050 deaths from lung cancer in 2018 as per the latest American Cancer Society's report. Alectinib, a more potent orally active tyrosine kinase inhibitor which was approved by the US Food & Drug Administration for anaplastic lymphoma kinase-positive lung adenocarcinoma, has been shown to have a reasonable safety profile when compared with other anaplastic lymphoma kinase-targeted therapy. As per research studies, grade 1 or 2 renal impairment has been reported but grade 4 renal toxicity due to alectinib has not been reported so far. We report a case of acute renal failure caused by alectinib which necessitated emergency dialysis. This is the first case report describing the severe renal toxicity of alectinib.

Case presentation: We describe a case of 72-year-old Taiwanese man diagnosed with stage IV anaplastic lymphoma kinase-positive adenocarcinoma of the lung initially treated with crizotinib for over a year, which was switched to alectinib due to disease progression with brain metastasis. Within 6 weeks of starting alectinib, he developed acute renal failure needing emergency dialysis support. His renal failure was secondary to acute tubular necrosis and had a complete reversal within 7-10 days on withdrawing the medication. When he was re-challenged with alectinib, his creatinine started to worsen again which confirmed the renal toxicity of alectinib.

Conclusions: This case emphasizes the uncommon adverse effect of the anaplastic lymphoma kinase-targeted therapy alectinib causing acute renal failure manifesting as acute tubular necrosis. Recognition of alectinib nephropathy requires a thorough drug history and knowledge of risk factors that lessen its margin of safety at therapeutic ingestions. Frequent monitoring of renal functions and early nephrology referral significantly reduce the mortality and morbidity of these patients.

Keywords: ALK rearrangement; Acute renal failure; Acute tubular necrosis; Adenocarcinoma; Alectinib; Case report; Non-small cell lung cancer.

PubMed Disclaimer

Conflict of interest statement

Ethics Approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Timeline of patient’s renal functions
See this image and copyright information in PMC

References

    1. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S-I, Watanabe H, Kurashina K, Hatanaka H. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561. doi: 10.1038/nature05945. - DOI - PubMed
    1. Kinoshita K, Asoh K, Furuichi N, Ito T, Kawada H, Hara S, Ohwada J, Miyagi T, Kobayashi T, Takanashi K, et al. Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802) Bioorg Med Chem. 2012;20:1271–1280. doi: 10.1016/j.bmc.2011.12.021. - DOI - PubMed
    1. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim D-W, Ou S-HI, Pérol M, Dziadziuszko R, Rosell R. Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med. 2017;377:829–838. doi: 10.1056/NEJMoa1704795. - DOI - PubMed
    1. Gilbert JA. Alectinib surpasses crizotinib for untreated ALK-positive NSCLC. Lancet Oncol. 2017;18:e377. doi: 10.1016/S1470-2045(17)30482-5. - DOI - PubMed
    1. Seto T, Kiura K, Nishio M, Nakagawa K, Maemondo M, Inoue A, Hida T, Yamamoto N, Yoshioka H, Harada M. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study. The Lancet Oncology. 2013;14:590–598. doi: 10.1016/S1470-2045(13)70142-6. - DOI - PubMed

MeSH terms