Steroid conference 2014

Diabetic macular edema (DME) is the most common cause of moderate vision loss in working-age individuals in developed countries. Corticosteroids reduce expression of VEGF and other permeability, providing good rationale for their use in DME. The first steroid used was the triamcinolone by intravitreal injection. Efficacy was good but the adverse events were rather important (elevated intraocular pressure being the most common). Different steroids implant with sustained ocular delivery are available. The Fluocinolone Acetonide for Macular Edema (FAME) studies permitted to the ILUVIEN® implant (190 µg) has received its marketing authorization approval in different European countries. It is indicated for the treatment of vision impairment associated with chronic DME, considered insufficiently responsive to available therapies. Dexamethasone Intravitreal Implant (OZURDEX®) provided long-term vision improvement, with a mean of injections over 3 years (phase III MEAD study). Its label is not yet obtained (March 2014). It safety profile was better or equivalent than that of steroids currently used in clinical practice. In summary, two platforms for sustained steroids drug delivery are available in DME.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor accounting for approximately 1% of sarcomas with an indolent growth and a less than 5% probability of metastases [ 45 ]. DFSP is characterized by the presence of distinctive, reciprocal rearrangement of chromosomes 17 and 22. The rearrangement leads to the fusion of alpha chain type a (COL1A1) localized on 17q22 to the platelet-derived growth factor beta (PDGFB) localized on 22q13. The formation of COL1A1-PDGFB fusion gene results in the constitutional upregulation of PDGFB expression, leading to continuous autocrine activation of PDGF receptor B (PDGFRB) which is a key pathogenetic factor [ 46 ]. Based on the inhibitory effects of Imatinib on DFSP cell growth in various in vitro and in vivo studies [ 47 ], initial case reports showed the benefit of Imatinib in metastatic and locally advanced DFSP [ 48 , 49 ]. In the largest retrospective series, 10 patients with locally advanced or metastatic DFSP received Imatinib 800 mg daily. All eight patients with locally advanced disease had karyotypic or fluorescence in situ hybridization (FISH) evidence of t(17;22), and all responded to therapy, two completely. The two patients with metastatic disease had more complex karyotypes. One who had the typical t(17;22) had a partial response that lasted seven months, while the second lacked the t(17;22) and did not respond [ 50 ]. It is not clear whether conventional DFSP tumors lacking t(17;22) respond as well to Imatinib. In neoadjuvant setting also, DFSP has been reported to be treated with Imatinib, with doses between 400 and 800 mg daily for a period ranging from 2 to 24 months (median, 4 months), producing an average tumor reduction of 50% (range: 19%–100%) after a median follow-up time of 24 months (range: 88 days to 72 months) [ 51 – 53 ]. Several questions remain regarding the mechanism of action of Imatinib and possible resistance to this targeted therapy in DFSP. However, Imatinib is currently the gold standard in the treatment of locally advanced or metastatic DFSP.

Steroid conference 2014

steroid conference 2014

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