Enfermedad de Paget en un grupo de pacientes hospitalarias

Se revisa la presentación de 9 (nueve) pacientes con enfermedad de Paget sobre un total de 278 pacientes con cáncer de mama (3,23 %), en un Servicio Hospitalario, durante un período de 5 (cinco) años. (Estudio restrospectivo randomizado). La Enfermedad de Paget es una rara variedad (hasta un 4% del total) de cáncer de mama que reside en el complejo teloareolar y que debe diferenciarse clínicamente del eczema, prurito o grieta del pezón, patologías benignas cuya signosintomatología es similar: prurito, edema, eczema, derrame serosanguinolento por el pezón, eritema y eventualmente, nodulo subareolar.Las pacientes fueron diagnosticadas clínica e histológicamente por biopsia incisional tridimensional (corte que incluye piel, tejido mamario y grasa). La estadificación es estándar para cáncer de mama. Una (1) de las pacientes se presentó en un estadio I de la clasificación TNM de la Organización Mundial contra el Cáncer (UICC), cinco (5) de las mismas correspondieron a un estadio lia y 3 (tres) presentaron un estadio III a y b. Todas las pacientes fueron tratadas de acuerdo a los protocolos oncológicos correspondientes al estadio. Dos pacientes fallecieron durante el seguimiento, pertenecientes al estadio III. Debe enfatizarse el diagnóstico diferencial de esta variedad de cáncer de  mama con patologías benignas de la aréola-pezón, a fin de tratar estas pacientes de acuerdo a las pautas de tratamiento del cáncer, evitando falsos negativos.

Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors

Background Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. Methods Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed. Results No DLTs occurred in parts A (n=18) or B (n=85). Grade 3–5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35). Conclusions Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy. Trial registration number NCT02043665

Approved checkpoint inhibitors in bladder cancer: which drug should be used when?

The treatment of advanced metastatic urothelial carcinoma has recently evolved with the approval of five checkpoint inhibitors. In the second-line setting, in patients who have progressed on cisplatin-based chemotherapy, pembrolizumab, atezolizumab, durvalumab, nivolumab and avelumab are United States Food and Drug Administration (FDA) approved. In cisplatin-ineligible patients, atezolizumab and pembrolizumab are the FDA-approved checkpoint inhibitors. Here we describe the updated clinical efficacy of these checkpoint inhibitors in the treatment of advanced urothelial carcinoma and then suggest how they can be sequenced in the context of available chemotherapeutic options. For cisplatin-eligible patients, platinum-based chemotherapy remains the standard first-line treatment. For patients progressing on platinum-based therapy, phase III trials have been performed comparing pembrolizumab and atezolizumab separately with standard chemotherapy, and results favor the use of pembrolizumab