A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT), a cornerstone of prostate cancer treatment, is commonly co-prescribed as combination therapy. OBJECTIVE: To better understand the safety and tolerability profile of relugolix, an oral non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, in combination with abiraterone acetate (abiraterone) and apalutamide, a phase I study was undertaken. PATIENTS AND METHODS: This is an ongoing, 52-week, open-label, parallel cohort study of relugolix in combination with abiraterone in men with metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC) [Part 1] and apalutamide in men with mCSPC or non-metastatic castration-resistant prostate cancer (nmCRPC) [Part 2]. Eligible patients treated with leuprolide acetate or degarelix with abiraterone or apalutamide prior to baseline, at which time they were transitioned to relugolix. Assessments included reporting of adverse events, clinical laboratory tests, vital sign measurements, electrocardiogram (ECG) parameters, and testosterone serum concentrations. In this interim report, patients completing ≥12 weeks were included. RESULTS: Overall, 15 men were enrolled in Part 1 and 10 in Part 2. Adverse events were mostly mild-to-moderate in intensity and were consistent with the known safety profiles of the individual medications. No transition (from prior ADT treatment)- or time-related trends in clinical laboratory tests, vital sign measurements, or ECG parameters were observed. Mean testosterone concentrations remained below castration levels. CONCLUSIONS: Combination therapy of relugolix and abiraterone or apalutamide was associated with a favorable safety and tolerability profile consistent with the known profiles of the individual medications. Castration levels of testosterone were maintained after transitioning to relugolix from other ADTs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04666129.

Partial Nephrectomy versus Thermal Ablation for Clinical Stage T1 Renal Masses: Systematic Review and Meta-Analysis of More than 3,900 Patients.

PURPOSE: A systematic review and meta-analysis of clinical trials was undertaken to compare percutaneous thermal ablation versus partial nephrectomy (PN) for stage T1 renal tumors. MATERIALS AND METHODS: A comprehensive search of major databases was conducted from October 2000 to July 2016. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Incidences of all-cause mortality (ACM), cancer-specific mortality (CSM), local recurrence (LR), and metastases, as well as complication rates and changes in estimated glomerular filtration rate (eGFR), were evaluated. RESULTS: Inclusion criteria were met by 15 of 961 papers. These studies represented 3,974 patients who had undergone an ablative procedure (cryoablation or radiofrequency ablation; n = 1,455; 37%) or PN (n = 2,519; 63%). ACM and CSM rates were higher for ablation than for PN (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.54-2.87 [P < .05]; HR, 3.84; 95% CI, 1.66-8.88 [P < .05], respectively). No statistically significant difference in LR rate or risk of metastasis was seen between ablation and PN (HR, 1.32; 95% CI, 0.79-2.22 [P = .22]; HR, 1.83; 95% CI, 0.67-5.01 [P = 0.23], respectively). Complication rates were lower for ablation than for PN (13% vs 17.6%; odds ratio, 0.49; 95% CI, 0.25-0.94; P < .05). A significantly greater decrease in eGFR was observed after PN (13.09 mL/min/1.73 m2) vs ablation therapy (4.47 mL/min/1.73 m2). CONCLUSIONS: Thermal ablation showed no significant difference in LR or metastases compared with PN. Thermal ablation was associated with a lower morbidity rate and a lesser reduction in eGFR compared with PN, but with higher ACM and CSM rates.

[Experience in the management of pediatric patients with Gaucher disease]. / Experiencia en el manejo de pacientes pediátricos con enfermedad de Gaucher.

Among lysosomal storage diseases, Gaucher disease depicts the highest rate of incidence, according with the international epidemiological reports. Gaucher disease is due to an impairing of the acid beta-glucosidase enzyme, since its lack promotes accumulation of the sphingolipid glucosylceramide at macrophages, leading to heterogeneous multiorganic damage (visceral, skeletal, and central nervous system affectation). This paper portrays a series of clinical cases of Gaucher disease with patients treated at the same city (Monterrey, Nuevo León), at the Paediatric Haematology Department of the Specialties General Hospital, UMAE 25, in Monterrey of the Instituto Mexicano del Seguro Social. Gaucher disease is symptomatic since early childhood in a good proportion of patients. The patients in this serie was treated with enzyme replacement therapy, and share the typical overall features of the disease.