Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

Shimada, Midori; Fukuda, Minoru; Fukuda, Masaaki; Kitazaki, Takeshi; Hashiguchi, Kohji; Ikeda, Takaya; Yamaguchi, Hiroyuki; Nakatomi, Katsumi; Ashizawa, Kazuto; Mukae, Hiroshi

doi:10.2147/ott.s136837

Cited by 10 publications

(13 citation statements)

References 18 publications

(19 reference statements)

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“…[12][13][14] On the other hand, the use of therapies targeting other driver oncogenes is recommended, regardless of the patient's age and general condition, because of the marked responses they induce and their mild toxicities. [15][16][17] However, the patient in the present case was 86 years old, which is classified as "oldest old", and the supportive care rates in this age group range from 55%-67%. 18,19 Despite this, it seems that the treatment caused an improvement in QOL and prolonged the patient's life by shrinking the tumor, and thus, it had meaningful effects.…”

Section: Discussionmentioning

confidence: 65%

“…Intensive treatment, such as combination chemotherapy or combined modality, does not usually produce a survival benefit in patients aged >70 or 75 years 12–14 . On the other hand, the use of therapies targeting other driver oncogenes is recommended, regardless of the patient's age and general condition, because of the marked responses they induce and their mild toxicities 15–17 . However, the patient in the present case was 86 years old, which is classified as “oldest old”, and the supportive care rates in this age group range from 55%–67% 18,19 .…”

Section: Discussionmentioning

confidence: 77%

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Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation

et al. 2020

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Dabrafenib and trametinib therapy for BRAF V600E-mutant non-small cell lung cancer (NSCLC) has demonstrated strong antitumor effects in clinical trials and has been approved for use in clinical practice. However, the efficacy and safety of this combination therapy in elderly patients remain unclear. An 86-year-old male patient, who had been diagnosed with lung adenocarcinoma with the BRAF V600E mutation, received dabrafenib and trametinib combination chemotherapy. The tumor shrunk rapidly; however, therapy was discontinued after 40 days because adverse events (hypoalbuminemia, peripheral edema, and pneumonia) developed. Although this targeted combination therapy seemed to cause relatively severe adverse events compared with single-agent targeted therapy in this "oldest old" elderly patient, the marked tumor shrinkage prolonged the patient's life and helped him to maintain a good general condition. Active targeted therapy may therefore be considered with appropriate drug dose reduction instead of conservative treatment, even if a patient is extremely old.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 77%

Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation

et al. 2020

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“…While the Anaplastic Lymphoma Kinase (ALK) inhibitor Crizotinib has been reported to be associated with acute kidney injury and chronic kidney disease, [1][2][3] the association with Alectinib is less well defined and merits further elucidation. [4][5][6] Alectinib is a second-generation highly selective oral Anaplastic Lymphoma Kinase (ALK) inhibitor approved by the FDA as first line therapy in ALK positive Non Small Cell Lung Carcinoma (NSCLC) and as second line therapy to Crizotinib resistant NSCLC. 6 Phase one studies of Alectinib in ALK-positive NSCLC reported increases in serum creatinine in 26% of participants, 6,7 and previous cases reported a temporal relationship between initiation of Alectinib and deterioration in kidney function without any other discernable cause, which improved with cessation of the agent.…”

Section: Discussionmentioning

confidence: 99%

Acute kidney Injury due to Alectinib, an Anaplastic Lymphoma Kinase inhibitor

Abdalla

Galambosi

et al. 2021

Journal of Onco-Nephrology

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Introduction: The array of unintended effects of targeted oncological treatments is still being elucidated. Cognizance of these effects is important since they allow early identification and intervention. Methods: We report a case of progressive reduction in kidney function following the introduction of the oral second generation Anaplastic Lymphoma Kinase (ALK) Inhibitor: Alectinib for the treatment of metastatic non-small cell carcinoma of the lung (NSCLC). Kidney biopsy findings suggested that the predominant manifestation was acute tubular injury, which resolved with cessation of Alectinib therapy and did not recur with the introduction of the third generation ALK inhibitor Lorlatinib. Conclusions: This case report adds to the Onco-Nephrology literature in relation to the potential nephrotoxic effects of ALK inhibitors.

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“…Nephrotoxicity associated with alectinib can be reduced by discontinuing the medication and re-challenging with a reduced dose to avoid dose-related nephrotoxicity [ 9 ]. The other measures which could reduce this complication would be to avoid volume depletion and dehydration in addition to avoiding the concomitant use of other nephrotoxic medications.…”

Section: Discussionmentioning

confidence: 99%

“…Our patient’s case demonstrates an extremely rare side effect of alectinib. Alectinib-induced nephrotoxicity has so far been reported in < 4% of patients in research studies [ 9 ]. Median time to cause grade III–IV renal impairment was around 4 months.…”

Section: Discussionmentioning

confidence: 99%

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

Ramachandran¹,

Morcus²,

Tahir³

et al. 2018

J Med Case Reports

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BackgroundLung 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 presentationWe 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.ConclusionsThis 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.

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Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

Cited by 10 publications

References 18 publications

Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation

Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation

Acute kidney Injury due to Alectinib, an Anaplastic Lymphoma Kinase inhibitor

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

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