Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome characterized by acute hypertension, headache, decreased level of consciousness, visual disturbances and seizures associated with characteristic neuroimaging changes indicative of vasogenic edema of the posterior cerebral white matter. Several medical conditions have been associated with PRES including hypertensive encephalopathy and eclampsia. The use of cytotoxic and immunosuppressant drugs, such as those which target vascular endothelial growth factor (VEGF), have also been implicated. We report here the case of a 71-year-old woman with metastatic clear cell renal carcinoma who developed PRES 3 months after commencing sorafenib. Elevated blood pressure (BP) was recorded, and MRI of the brain) of the brain showed asymmetric areas of increased signal intensity within the supratentorial white matter suggestive of PRES. Clinical and radiological features rapidly improved with BP control and discontinuation of sorafenib. Sorafenib was resumed with no sign of PRES recurrence. The present case report supports the hypothesis that, in selected patients, the re-introduction of anti-VEGF therapies after PRES is feasible.
This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel.
In this age group, the specificity of ADC was found superior to that of the CDC. The clinical use of the ADC might be associated with less useless diagnosis procedures, without significant increase in rate of diagnosis failure.
Introduction: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL) wherein those with advanced stage have a poor prognosis, severe skin manifestations, blood and/or lymph node involvement, and compromised survival. The aim of this study was to describe patient clinical characteristics, management and survival in MF patients who were refractory or had relapsed after a first systemic therapy across 5 European countries.
Methods:A retrospective multicenter chart review study was conducted at 19 European sites. Patient data were pseudonymized following both central & local Ethics Committees approval. Inclusion criteria allowed patients to enrol if they had a first diagnosis of MF and proved to be relapsed/refractory (R/R) prior to 1-Jan-2016 after a first course of systemic therapy. Overall survival (OS) was estimated from the date of R/R (defined here as index date) using Kaplan-Meier estimates. Results: This analysis included 69 R/R MF patients with a median follow-up of 3.9 (range: 0.1-16.9) years from the index date. The median age at index date was 60.0 (range: 22-84) years. After R/R 68 (98.6%) patients received further treatment including systemic therapies in routine practice (91.2%), allogeneic stem-cell transplant (1.5%) and treatment within a clinical trial (7.3%). At treatment initiation following R/R, the majority of patients had advanced stage, i.e. IIB-IVB (64.3%) as per the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer. At index date 45 patients (66.2%) had one or more new lymphoma lesions, mostly associated with MF subtype but other new subtypes were observed in a small number of patients. The presence of large cell transformation was detected in 12.5% at index date. In total 72.1% of patients became refractory or relapsed again at end of therapy in R/R, with a median time to next R/R of 15.8 (range: 0.6-174.6) months. In total, 27 deaths (39.1%) were observed during the study, with a median age at death of 65 (range: 50-85) years. The majority of patients (74.1%) died from CTCL, CTCL complications, or toxicity from treatment of CTCL. The estimated median OS was 11.5 years (95% CI: 6.5not reached [NR]) from time of R/R in this MF population (Figure). There were some differences in trends in OS according to treatment received for R/R, with single and combination chemotherapies having an estimated median OS of 6.5 years (95% CI: 2.25 -NR) compared to NR (95% CI: 12.1 -NR) for the other systemic therapies (i.e. retinoids, methotrexate, interferon and photopheresis).Conclusions: This analysis from an observational study in treated R/R MF who previously received one systemic therapy estimates median OS at 12 years. The high rate of relapse suggests that the clinical burden of R/R MF is significant in Europe, and in this context recently approved targeted therapies have the potential of improving outcomes
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