Репозиторий Университета

© 2018 UICC The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m2) in 28-day cycles to identify the recommended phase II dose (RP2D) of pimasertib. In the phase II part, patients were randomised to pimasertib (RP2D) or placebo plus weekly gemcitabine (n = 88) to investigate progression-free survival (PFS), overall survival (OS) and safety. The RP2D was determined to be 60 mg BID. PFS and OS outcomes did not indicate any treatment benefit for pimasertib over placebo in combination with gemcitabine (median PFS 3.7 and 2.8 months, respectively, HR = 0.91, 95% CI: 0.58–1.42: median OS 7.3 vs. 7.6 months, respectively). KRAS status did not influence PFS or OS. The incidence of grade ≥3 adverse events was 91.1% and 85.7% for pimasertib/gemcitabine and placebo/gemcitabine respectively, but there was a higher incidence of ocular events with pimasertib/gemcitabine (28.9% vs. 4.8% for placebo/gemcitabine). In conclusion, no clinical benefit was observed with first-line pimasertib plus gemcitabine compared with gemcitabine alone in patients with mPaCa.

PURPOSE: To evaluate various methods of stripping Descemet's membrane of a donor corneoscleral flap for Descemet's membrane endothelial keratoplasty (DMEK). MATERIAL AND METHODS: The study included 60 corneoscleral flaps (mean donor age was 62.9 years) from the eye bank of Research Institute of Eye Diseases, which were not suitable for clinical use due to positive serological results. Four alternative methods of donor material dissection in preparation for DMEK were compared: SCUBA (group A), our newly suggested method utilizing intracapsular ring (group B), 'liquid bubble' (group C), 'big bubble' (group D). Parameters under evaluation were mean transplant preparation time, density of endothelial cells before and after dissection, presence of complications during detachment of Descemet's membrane. RESULTS: Mean detachment time in group A was 8.5 min, in group B - 7 min, in group C - 8 min, and in group D - 5 min. Loss of endothelial cells as compared with baseline was in average 10.5% in group A, 9.3% in group B, 10.7% in group C, and 10.3% in group D. Group A had two cases with complications occurring during separation of Descemet's membrane, group B had one such case, group C - 2 cases, and group D - 3 cases. Histologic examination confirmed absence of stromal fibers on the detached Descemet's membrane in groups A, B and C. CONCLUSION: Among the described methods of preparing donor material for DMEK surgery, all except 'big bubble' proved equal in terms of resulting transplant quality. The 'big bubble' dissection technique requires more time to complete, while the resulting transplant has stromal fibers. Our newly suggested method of Descemet's membrane stripping that utilizes intracapsular ring proved safe and effective alternative for preparing donor material for DMEK.