AZ191 Principles Defined

F. R. J. was the recipient of a Canada Research Chairs award. Conflict of Interest None declared.""Crizotinib is a potent and selective small-molecule inhibitor of the receptor tyrosine kinases (RTKs) anaplastic lymphoma kinase (ALK), hepatocyte growth factor (HGF) receptor (MET), ROS1, and RON (Pfizer Inc., data on file).1,2 ALK gene rearrangement (ALK-positivity) occurs in 4% to 7% of patients with non�Csmall cell lung cancer (NSCLC).3�C6 In a randomized phase III study in previously treated ALK-positive NSCLC (PROFILE 1007), crizotinib Apoptosis Compound Library manufacturer treatment was shown to be superior to standard single-agent chemotherapy (pemetrexed or docetaxel) in prolonging progression-free survival.7 Crizotinib has now been approved in over 70 countries for the treatment of locally advanced or metastatic ALK-positive NSCLC. The first serious adverse event (SAE) comprising a complex renal cyst developing during crizotinib treatment was reported in a phase II study of crizotinib 250?mg twice daily in patients with ALK-positive NSCLC (PROFILE 1005) in January 2011 (patient 1, Table ?Table1).1). Additional cases were reported subsequently, prompting consideration of a causal association with crizotinib. Among 1205 patients who AZ191 received crizotinib in the two largest crizotinib clinical trials (PROFILE 1005 and PROFILE 1007) through 10 September 2012, 24 patients (2%) had AE reports of treatment-related renal cysts. To our knowledge, this is the first time that a tyrosine kinase inhibitor has been associated with renal cyst development. Table 1 Summary of cases of renal cysts reported as serious adverse events Cysts are the most common space-occupying lesion of the kidneys and are classified as either simple or complex. Simple cysts are round or oval in shape and are typically lacking internal echoes, calcification, or enhancement.8 Septations, if present, are limited to one or two.9 Simple cysts are usually asymptomatic, are frequently diagnosed incidentally, and are commonly encountered in the general population, with reported prevalences of up to 41%.10 The prevalence, size, and bilaterality of renal cysts increases with advancing age, and cysts tend to be more common in men than women.10,11 At least some of the differences in the prevalence rates reported over time may be due to the recent emergence of more advanced imaging Selleckchem LGK 974 techniques.12 Complex renal cysts are relatively uncommon (prevalence