crizotinib and Kidney-Diseases--Cystic

Crizotinib is a first-generation tyrosine kinase inhibitor used for anaplastic lymphoma kinase (ALK) positive cancers. Simple and complex renal cyst formation is a rare complication of crizotinib use that has been reported previously in the adult population.. We report a case of a right renal mass in a 17-year-old with ALK-positive epithelioid inflammatory myofibroblastic sarcoma treated with Crizotinib. After cessation of Crizotinib and initiating Alectenib, a second generation ALK inhibitor, the mass decreased in size and the patient remained asymptomatic without evidence of recurrence at three months of follow-up.

Topics: Adolescent; Antineoplastic Agents; Crizotinib; Humans; Kidney Diseases, Cystic; Male; Neoplasms, Muscle Tissue; Receptor Protein-Tyrosine Kinases; Sarcoma

The oral small-molecule tyrosine kinase inhibitor (TKI), crizotinib has been approved as a first-generation anaplastic lymphoma kinase (ALK) inhibitor in treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). Recently, development of complex renal cysts has been reported with crizotinib usage, highlighting the importance of accurate differentiation between complex renal cysts and new metastasis in NSCLC. Here we describe a case study with confirmed EGFR wild-type and ALK-rearranged lung adenocarcinoma who developed complex renal cysts combined with hemorrhage during crizotinib treatment, with no abnormal clinical symptoms or kidney functions observed. Interestingly, without crizotinib treatment termination or reduction, the complex hemorrhagic renal cysts regressed with self-limiting and healing. The combined usage of ultrasound, CT and MRI techniques in the presented case allowed proper monitoring of the internal changes within complex renal cysts. The patient provided written informed consent authorizing publication of clinical case. Thus, better understanding of the imaging features of crizotinib-related renal cysts combined with hemorrhage would avoid misdiagnoses as a new metastatic renal mass or the aggravation of the primary disease, therefore avoiding further invasive investigation.

Topics: Adenocarcinoma; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Crizotinib; Female; Hemorrhage; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Magnetic Resonance Imaging; Middle Aged; Ultrasonography

Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that was approved for ALK-harboring lung cancer. There have been reports about the development and progression of renal cysts from crizotinib. We report a series of 3 cases of crizotinib-associated renal cysts in patients admitted to our institution, with different kinds of presentation. A monitor for complex renal cysts is warranted in patients receiving crizotinib.

Topics: Aged; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Crizotinib; Female; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Male; Protein Kinase Inhibitors

Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer. This targeted cancer therapy agent has been shown to have superior efficacy over standard chemotherapy in this small subset of lung cancer patients. An adverse effect of this drug therapy is the development of complex renal cysts. Here, we present a case of a 68-year-old patient with non-small cell lung cancer on Crizotinib therapy who developed complex bilateral renal cysts. It is important to recognize this drug-related complication in order to avoid mistaking it for disease progression, primary renal malignancy, or renal infection.

Topics: Aged; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Kidney Diseases, Cystic; Kidney Neoplasms; Lung Neoplasms; Male; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases

Topics: Antineoplastic Agents; Crizotinib; Female; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Middle Aged

Topics: Antineoplastic Agents; Carbazoles; Crizotinib; Humans; Kidney Diseases, Cystic; Piperidines

Crizotinib is highly effective against anaplastic lymphoma kinase-positive and c-ros oncogen1-positive non-small cell lung cancer. Renal dysfunction is associated with crizotinib therapy but the mechanism is unknown. Here, we report a case of anaplastic lymphoma kinase positive non-small cell lung cancer showing multiple cysts and dysfunction of the kidneys during crizotinib administration. We also present results demonstrating that long-term crizotinib treatment induces fibrosis and dysfunction of the kidneys by activating the tumor necrosis factor-α/nuclear factor-κB signaling pathway. In conclusion, this study shows the renal detrimental effects of crizotinib, suggesting the need of careful monitoring of renal function during crizotinib therapy.

Topics: Aged; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Fibrosis; Humans; Kidney; Kidney Diseases; Kidney Diseases, Cystic; Lung Neoplasms; Mice

Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation. Switching to alectinib may be beneficial in patients demonstrating crizotinib-associated complex renal cysts with systemic inflammation and exhaustion.

Topics: Adenocarcinoma; Antineoplastic Agents; Carbazoles; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases; Treatment Outcome

Novel therapeutic agents recently introduced for the treatment of cancer have several unusual side effects. An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib. Many of these lesions undergo spontaneous resolution despite developing complex features on imaging. We assess the incidence and patterns of evolution of Crizotinib Associated Renal Cysts [CARCs] at our institute and provide histopathology correlation of their benign nature.. A retrospective analysis of renal lesions in computerised tomography (CT) scans of 35 patients with advanced ALK-rearranged NSCLC who had been prescribed crizotinib at our institution was performed by three radiologists, who analysed the evolution of these lesions, particularly for pre-defined significant and complex changes.. Of 26 patients eligible for this analysis, 4 (15%) had cysts at baseline that remained stable on crizotinib treatment while 11(42%) developed significant change in 28 renal cysts. Commonest pattern of cyst evolution was enlargement from baseline followed by spontaneous regression (17/28 lesions) while other patterns noted were stable lesions, regression from baseline and ongoing enlargement. The median maximum size reached was 23 mm (range 9 - 67 mm) after a median of 178 days (160 to 1342) on crizotinib. Complex change occurred in 12 cysts, in 7/26 (27%) patients and within 60 days of starting Crizotinib in 10 cysts. Imaging features were falsely concerning for malignancy or abscess in 4/26 patients.. Most CARCs resolve spontaneously, or have a benign evolution despite enlargement and other features concerning for malignancy or infection on imaging. This unusual manifestation of chemotherapy should be recognised, particularly by radiologists, so that inappropriate treatment decisions are avoided.

Topics: Adult; Aged; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Incidence; Kidney Diseases, Cystic; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Tomography, X-Ray Computed

Treatment with the ALK inhibitor crizotinib has been associated with complex renal cyst formation in patients with non-small cell lung cancer (NSCLC). Using patients treated with crizotinib, we aimed to evaluate the incidence of renal cyst formation, to identify risk factors for cyst formation and to provide a radiological description of cyst characteristics. Patients with ALK-positive NSCLC treated with crizotinib were retrospectively identified from an institutional database. Computed tomography (CT) imaging performed prior to and during crizotinib treatment was retrospectively reviewed to assess the size and complexity of pre-existing cysts, new cysts, and enlarging cysts. Demographic data including age, sex, ethnicity, smoking history and length of treatment were also recorded. Data from 60 patients with NSCLC treated with crizotinib at our institution between 6/5/2009 and 7/1/2015 were collected. 57 had CT imaging before and during treatment. Mean length of imaging follow-up was 18 months. 9 (16%) patients had cysts which enlarged or developed de novo during treatment. 2 (4%) patients developed complex renal cysts (1 of these patients also developed complex hepatic cysts). Female gender (p=0.008) and the presence of renal cysts on baseline scans (p=0.044) were significantly associated with cyst formation or growth. Renal cyst formation or growth occurred in 16% of crizotinib-treated patients. Women and those with pre-existing cysts were at greatest risk. Although the potential causal relationship between crizotinib use and renal cyst formation has yet to be fully defined, it is important for radiologists and clinicians to be aware of this finding.

Topics: Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Follow-Up Studies; Humans; Incidence; Kidney Diseases, Cystic; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed

Crizotinib is the first clinically available tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and is associated with the development of complex renal cysts. We now describe a 39-year-old woman who developed infected complex renal cysts during crizotinib treatment. After 10 months of such treatment, she presented with a high fever and low back pain. Computed tomography findings were consistent with complex renal cysts and perilesional inflammation. Interventions including cyst drainage and antibiotic administration contributed to diagnosis and management of the infected cysts.

Topics: Adult; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases; Tomography, X-Ray Computed

An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Serious adverse event (SAE) reports of renal cysts from a safety database of 1375 patients from four clinical trials were reviewed. A blinded, retrospective, independent radiologic review (IRR) was performed using scans from patients on study for ≥ 6 months in three clinical trials; risk factors for renal cyst development were assessed. Among 17 patients with renal cysts reported as SAEs, evidence of invasion into adjacent structures was noted in seven patients, with no evidence of malignancy found. These patients generally did not require dose reductions, none required permanent crizotinib discontinuation due to this AE, and most continued treatment with clinical benefit. In the blinded IRR, among 255 crizotinib-treated patients, 22%, 3%, and 2% had preexisting simple cysts, complex cysts, or both, respectively. At the 6-month tumor assessment, 9% of all patients had acquired new cysts, and 2% of patients with preexisting cysts had developed new cysts and enlargements (>50%) of preexisting simple cysts. Asians appeared to have an increased risk of developing new cysts on treatment; Koreans in particular had 5.18 times higher odds of developing cysts than non-Asians (95% confidence interval, 1.51-17.78; P = 0.05). Crizotinib treatment appears to be associated with an increased risk of development and progression of renal cysts in patients with ALK-positive NSCLC. While close monitoring is recommended, dosing modification was not generally necessary, allowing patients to remain on crizotinib treatment.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome

We report the case of a woman with an ALK positive lung adenocarcinoma, who developed bilateral complex renal cysts 17 months after the introduction of treatment with crizotinib. Clinical investigation led to the conclusion that the cysts were due to anticancer drug. Regression of the renal cysts was observed one month after cessation of the crizotinib. This case illustrates that specific and little known toxicities can occur with these novel molecules which have entered use for the management of lung cancer.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Antineoplastic Agents; Bone Neoplasms; Crizotinib; Female; Humans; Kidney Diseases, Cystic; Lung Neoplasms; Protein Kinase Inhibitors; Pyrazoles; Pyridines

Topics: Carcinoma, Non-Small-Cell Lung; Crizotinib; Cysts; Female; Humans; Kidney; Kidney Diseases, Cystic; Middle Aged; Pyrazoles; Pyridines

The development of complex renal cysts after crizotinib treatment for non-small-cell lung cancer (NSCLC) is a reported side effect. However, its occurrence and characteristics have not been reported.. Medical records and computed tomography images of crizotinib-treated patients in three prospective clinical trials were reviewed. The size and Bosniak category of the renal cysts before and after crizotinib treatment were determined. Patients' clinical characteristics, tumor stage, treatment response, renal function, and outcomes were analyzed.. During December 2010 to March 2013, we enrolled 32 patients who received crizotinib. There were 23 patients who had renal cysts before crizotinib. The median follow-up time was 493 days. Seven patients (22%, six with baseline renal cyst and one without baseline renal cyst) had significant renal cyst change. Four (13% of all) had new complex renal cysts. The median time from crizotinib treatment to first recognization of significant renal cyst change was 77 days. After stopping crizotinib, complex renal cysts regressed significantly. Patients with significant renal cyst change received more previous anticancer therapy (median, 5 lines versus 3 lines, p = 0.04) and received crizotinib for longer duration (median, 956 days versus 248 days, p = 0.007) compared with those without significant renal cyst change.. Change of renal cysts after crizotinib treatment is not uncommon. Development of complex renal cysts reverses after stopping crizotinib.

Topics: Adult; Aged; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Kidney; Kidney Diseases, Cystic; Lung Neoplasms; Male; Middle Aged; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases