pazopanib and Proteinuria

As precision medicine has become a focus in oncology in recent years, many targeted and biologic agents are being used along with or in place of traditional cytotoxic chemotherapy. As these drugs have been developed and some have received FDA approval, we have gained substantial data about the adverse event profiles. However, the management and approach to the toxicities incurred and subsequent complications are often not well understood, especially for physicians who have a varied clinical practice. The purpose of this review is to provide an overview of the frequency and types of adverse events and appropriate management steps when prescribing modern targeted therapies for gynecologic cancers in the classes of anti-angiogenic agents, poly-ADP-ribose polymerase (PARP) inhibitors, and immunotherapy drugs.

Topics: Anemia; Angiogenesis Inhibitors; Antineoplastic Agents, Immunological; Autoimmune Diseases; Bevacizumab; Diarrhea; Epistaxis; Fatigue; Female; Genital Neoplasms, Female; Headache; Hemorrhage; Humans; Hypertension; Indazoles; Intestinal Perforation; Molecular Targeted Therapy; Nausea; Neutropenia; Poly(ADP-ribose) Polymerase Inhibitors; Precision Medicine; Proteinuria; Pyrimidines; Risk Assessment; Sulfonamides; Vomiting; Water-Electrolyte Imbalance

Vascular endothelial growth factor receptor inhibitors, mammalian target of rapamycin inhibitors, and tyrosine kinase inhibitors are approved for metastatic renal cell cancer. Proteinuria can occur, but there is limited data regarding the incidence, monitoring, and management in metastatic renal cell cancer patients.. Our primary objective was to describe the incidence and severity of proteinuria in metastatic renal cell cancer patients treated in the first-line setting with pazopanib, bevacizumab, or everolimus.. We conducted a retrospective review of patients with metastatic renal cell cancer enrolled from January 2011-April 2013 in a phase II trial. Baseline and toxicity data were extracted from the electronic medical record. Descriptive statistics were used.. In all, 129 patients were eligible for analysis. The overall incidence of proteinuria was 81%, with most events being Grade 1 or 2. The incidence of proteinuria was 80% (n = 35) for pazopanib, 64% (n = 25) for bevacizumab, and 96% (n = 44) for everolimus. At peak proteinuria, 80% (n = 28), 64% (n = 16), and 80% (n = 35) of patients on pazopanib, bevacizumab, and everolimus, respectively, were managed with continued monitoring at the same dose. The overall incidence of Grades 3 and 4 events was 24% (n = 6) and found in the bevacizumab group.. A high incidence of proteinuria with minor severity within each class was demonstrated. It may be reasonable to continue therapy at the same dose for Grade 1 or 2 proteinuria. Treatment modification or discontinuation of therapy may be warranted with Grade 3 or 4 proteinuria.

Topics: Adult; Aged; Antineoplastic Agents; Bevacizumab; Carcinoma, Renal Cell; Cohort Studies; Everolimus; Female; Humans; Indazoles; Kidney Neoplasms; Male; Middle Aged; Prospective Studies; Proteinuria; Pyrimidines; Retrospective Studies; Sulfonamides

Proteinuria is a common adverse effect of vascular endothelial growth factor targeted agents, particularly in metastatic renal cell carcinoma (mRCC). However, risk factors for proteinuria are poorly defined.. Data on 1392 mRCC patients using pazopanib or sunitinib were pooled from two Phase-III clinical trials. Risk factors and prognostic effect of on-therapy proteinuria were evaluated by Cox proportional hazards regression.. Any-grade (1-4) and grade 3/4 proteinuria incidence were 15.0% and 3.7%, respectively. Asian ethnicity, diabetes, baseline systolic blood pressure (SBP), pre-existing grade 1 proteinuria and prior nephrectomy were significant independent predictors of either any-grade or grade 3/4 proteinuria. Proteinuria, particularly grade 3/4 (adjusted hazard ratio 0.53 (95% confidence interval 0.30-0.92)), was associated with improved overall survival.. In mRCC patients using pazopanib or sunitinib, Asian ethnicity, diabetes, SBP, pre-existing proteinuria and prior nephrectomy were independent predictors of on-therapy proteinuria, which was associated with improved survival.

Topics: Carcinoma, Renal Cell; Female; Humans; Indazoles; Indoles; Kidney Neoplasms; Male; Middle Aged; Proportional Hazards Models; Proteinuria; Pyrimidines; Pyrroles; Risk Factors; Sulfonamides; Sunitinib; Survival Analysis; Vascular Endothelial Growth Factor A

Pazopanib has been reported to induce proteinuria; however, no pathological findings have been reported. We herein report the case of a 31-year-old man with rhabdomyosarcoma treated with pazopanib who developed nephrotic syndrome. A renal biopsy revealed endothelial injury with podocyte changes. Based on the biopsy findings, we diagnosed the patient with nephrotic syndrome caused by pazopanib. Following the discontinuation of pazopanib, the patient's proteinuria gradually decreased without any specific treatment. We should be careful when encountering drug-induced proteinuria in patients taking pazopanib.

Topics: Adult; Humans; Indazoles; Male; Nephrotic Syndrome; Podocytes; Proteinuria; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Rhabdomyosarcoma; Sulfonamides