Crizotinib and renal insufficiency: A case report and review of the literature

doi:10.1016/j.lungcan.2014.03.001

Lung Cancer

Volume 84, Issue 3, June 2014, Pages 310-313

https://doi.org/10.1016/j.lungcan.2014.03.001 Get rights and content

Abstract

A 69 year old man with idiopathic chronic kidney disease was diagnosed with relapsing EGFR negative, ALK positive lung adenocarcinoma, and treated with chemotherapy and antiangiogenic treatment, under which his renal insufficiency worsened. During second line crizotinib treatment, further worsening of the renal function was seen, with very clear correlation with crizotinib withdrawal and rechallenge. No further drug causes for the worsening blood creatinine values were detected.

Introduction

Crizotinib treatment has become a very important treatment for ALK translocated metastatic adenocarcinoma of the lung, showing much higher responses and longer time to disease progression as compared to conventional chemotherapy regimens [1], [2], [3]. However, due to its accelerated approval in 2011 based mainly on phase I data, we are still in the process of acquiring knowledge on its toxicity profile and consequences on the long run. As with many other targeted therapies, this will be achieved through prolonged treatment of a higher number of patients.

We report on a case of worsening chronic kidney disease under crizotininb treatment, and review the data on the subject.

Section snippets

Case

A 69 year old man, 59 kg and 160 cm, presented in 2006 with a fetal type adenocarcinoma of the lung. As medically relevant history he referred an ischemic ictus two months before the oncologic diagnosis, mild blood hypertension without pharmacologic treatment at that point, diabetes mellitus type 2, benign prostate hyperplasia and a past smoking history of 35 pack years. He underwent a superior right lobectomy which confirmed a radiologically staged fetal type adenocarcinoma of the lung pT1 pN0

Discussion

The upcoming use of targeted therapies has confronted us with new and partially unknown secondary effects. It has been suggested that co-expression of shared targets between normal tissues and tumoral cells could underlie and explain some of these toxicities. Vascular endothelial growth factor (VEGF), for instance, the target of bevacizumab therapy, is strongly expressed in the embryologic developmental phase and plays a major role in vessel formation at that stage. It is further highly

Conflict of interest statement

None declared.

References (10)

D.R. Camidge et al.
Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase I study
Lancet
(2012)
X. Zhu et al.
Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis
Am J Kidney Dis
(2007)
L. Gastaud et al.
Acute kidney injury following crizotinib administration for non-small-cell lung adenocarcinoma
Lung Cancer
(2013)
E.L. Kwak et al.
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer
N Engl J Med
(2010)
A.T. Shaw et al.
Crizotinib versus chemotherapy in advanced ALK-positive lung cancer
N Engl J Med
(2013)

There are more references available in the full text version of this article.

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Case reportCrizotinib and renal insufficiency: A case report and review of the literature

Abstract

Introduction

Section snippets

Case

Discussion

Conflict of interest statement

Lancet

Am J Kidney Dis

Lung Cancer

Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer

N Engl J Med

Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

N Engl J Med

Case report
Crizotinib and renal insufficiency: A case report and review of the literature