Acute Tubular Injury and Renal Arterial Myocyte Vacuolization Following Crizotinib Administration

Abstract

INTRODUCTION C onsiderable part (19.4%) of the total cancer deaths (1.59 million deaths worldwide) in 2012 were related to lung cancer. It is estimated that more than 200,000 new cases of lung cancer will develop and up to 158,000 resulting deaths will ensue. Out of this large number, non–small cell Lung cancer (NSCLC) presents itself as the most common lung cancer (90%) and is associated with significant morbidity and mortality. Amid the genetic characteristics of NSCLC, echinoderm microtubule-associated protein-like 4 (EML4)–anaplastic lymphoma kinase (ALK) mutation, which translates into a fusion-type protein tyrosine kinase, offers a promising therapeutic interest. This mutation occurs in a distinct subgroup of NSCLC patients (3%–5%) and generally presents in patients who have histology characteristic of adenocarcinoma, are younger, and have little or no smoking history. Crizotinib is the first synthesized member of the ALK inhibitor family targeting this ALK mutation. It was approved by the US Food and Drug Administration for ALK inhibition in NSCLC. Phase III trials (PROFILE 1007, PROFILE 1014) confirmed the superior efficacy of crizotinib in the treatment of ALK-positive NSCLC. As with other recently released targeted agents, renal adverse renal effects have been observed (Table 1), including acute kidney injury (AKI) (Camidge DR, Bang Y, Kwak EL, et al. Progression-free survival (PFS) from a phase 1 study of crizotinib (PF02341066) in patients with ALK positive non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2011;29(Suppl):abstract 2501). We came across a special case of worsening chronic kidney disease under crizotinib treatment with 2 characteristics: AKI and acute tubular injury occurred late, almost 1 year after crizotinib initiation, and histologically, by the presence of unusual arteriolar myocyte vacuolization.