المساهمون: Sung-Gyu Lee, Long-Bin Jeng, Faouzi Saliba, Arvinder Singh Soin, Wei-Chen Lee, Paolo De Simone, Frederik Nevens, Kyung-Suk Suh, Lutz Fischer, Dong Jin Joo, John Fung, Jae-Won Joh, Toshimi Kaido, David Grant, Matthias Meier, Barbara Rauer, Carole Sips, Shuhei Kaneko, Gary Levy, Joo, Dong Jin

مصطلحات موضوعية: Adult, Calcineurin Inhibitors / administration & dosage, Calcineurin Inhibitors / adverse effects, Carcinoma, Hepatocellular / diagnosis, Hepatocellular / surgery, Drug Therapy, Combination, Everolimus / administration & dosage, Everolimus / adverse effects, Female, Glomerular Filtration Rate / drug effects, Graft Rejection / diagnosis, Graft Rejection / immunology, Graft Rejection / prevention & control, Graft Survival / drug effects, Humans, Immunosuppressive Agents / administration & dosage, Immunosuppressive Agents / adverse effects, Kidney / drug effects, Kidney / physiopathology, Liver Neoplasms / diagnosis, Liver Neoplasms / surgery, Liver Transplantation* / adverse effects, Male, Middle Aged, Randomized Controlled Trials as Topic, Recurrence, Tacrolimus / administration & dosage, Tacrolimus / adverse effects

الوصف: Background and methods: Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24. Results: EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, -1.0%; 95% confidence interval, -5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (-8.37 versus -13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (-12.82 versus -17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels. Conclusions: EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results. ; open

العلاقة: TRANSPLANTATION; J02754; OAK-2021-08802; https://ir.ymlib.yonsei.ac.kr/handle/22282913/187238Test; T202105332; TRANSPLANTATION, Vol.105(7) : 1564-1575, 2021-07

الإتاحة: https://doi.org/10.1097/TP.0000000000003394Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187238Test

المساهمون: Robert Motzer, Boris Alekseev, Sun-Young Rha, Camillo Porta, Masatoshi Eto, Thomas Powles, Viktor Grünwald, Thomas E Hutson, Evgeny Kopyltsov, María J Méndez-Vidal, Vadim Kozlov, Anna Alyasova, Sung-Hoo Hong, Anil Kapoor, Teresa Alonso Gordoa, Jaime R Merchan, Eric Winquist, Pablo Maroto, Jeffrey C Goh, Miso Kim, Howard Gurney, Vijay Patel, Avivit Peer, Giuseppe Procopio, Toshio Takagi, Bohuslav Melichar, Frederic Rolland, Ugo De Giorgi, Shirley Wong, Jens Bedke, Manuela Schmidinger, Corina E Dutcus, Alan D Smith, Lea Dutta, Kalgi Mody, Rodolfo F Perini, Dongyuan Xing, Toni K Choueiri, Rha, Sun Young

مصطلحات موضوعية: Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized / administration & dosage, Humanized / adverse effects, Antineoplastic Agents / adverse effects, Antineoplastic Agents / therapeutic use, Antineoplastic Combined Chemotherapy Protocols / adverse effects, Antineoplastic Combined Chemotherapy Protocols / therapeutic use, Carcinoma, Renal Cell / drug therapy, Renal Cell / mortality, Everolimus / administration & dosage, Everolimus / adverse effects, Female, Humans, Kidney Neoplasms / drug therapy, Kidney Neoplasms / mortality, Male, Middle Aged, Phenylurea Compounds / administration & dosage, Phenylurea Compounds / adverse effects, Programmed Cell Death 1 Receptor / antagonists & inhibitors, Progression-Free Survival, Protein Kinase Inhibitors / therapeutic use, Quinolines / administration & dosage, Quinolines / adverse effects, Sunitinib / adverse effects

الوصف: Background: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. Methods: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. Results: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included ...

العلاقة: NEW ENGLAND JOURNAL OF MEDICINE; J02371; OAK-2021-06182; https://ir.ymlib.yonsei.ac.kr/handle/22282913/185460Test; T202104165; NEW ENGLAND JOURNAL OF MEDICINE, Vol.384(14) : 1289-1300, 2021-04

الإتاحة: https://doi.org/10.1056/NEJMoa2035716Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/185460Test

المساهمون: Franco Citterio, Mitchell Henry, Dean Y Kim, Myoung Soo Kim, Duck-Jong Han, Takashi Kenmochi, Eytan Mor, Giuseppe Tisone, Peter Bernhardt, Maria Pilar Hernandez Gutierrez, Yoshihiko Watarai, Kim, Myoung Soo

مصطلحات موضوعية: Adult, Calcineurin Inhibitors / administration & dosage, Calcineurin Inhibitors / adverse effects, Everolimus / administration & dosage, Everolimus / adverse effects, Female, Humans, Immunosuppressive Agents / administration & dosage, Immunosuppressive Agents / adverse effects, Incidence, Kidney Transplantation, Lymphocele / epidemiology, Lymphocele / etiology, Male, Middle Aged, Mycophenolic Acid / administration & dosage, Mycophenolic Acid / adverse effects, Risk, Surgical Wound Dehiscence / epidemiology, Surgical Wound Dehiscence / etiology, Wound Healing / drug effects, Calcineurin inhibitor, everolimus, randomized, safety, wound healing

الوصف: Objectives: In TRANSFORM, de novo kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3-8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15. Methods: Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19. Results: The safety population consisted of 2,026 patients (EVR+rCNI: 1,014, MPA+sCNI: 1,012). The proportion of patients with at least 1 WHAE was comparable between EVR+rCNI and MPA+sCNI treatment groups [20.6% vs. 17.3%; risk ratio (RR): 1.19; 95% confidence interval (CI): 0.99, 1.43] at month 24. The numerical difference between EVR+rCNI and MPA+sCNI was mainly caused by an increased proportion of EVR patients with lymphocele and wound dehiscence [7.5% vs. 5.1% (RR: 1.46; 95% CI: 1.04, 2.05) and 3.9% vs. 1.8% (RR: 2.22; 95%CI: 1.28, 3.84), respectively] 20. Conclusion: The immediate introduction of EVR+rCNI after kidney transplantation was associated with an overall comparable incidence of WHAEs versus current standard-of-care over the 24-month study period. There was an increased relative risk of experiencing lymphocele and wound dehiscence but the absolute risks were rather low in both groups 21. Ct.gov identifier: NCT01950819. ; restriction

العلاقة: EXPERT OPINION ON DRUG SAFETY; J03925; OAK-2021-05745; https://ir.ymlib.yonsei.ac.kr/handle/22282913/185010Test; T999202325; EXPERT OPINION ON DRUG SAFETY, Vol.19(10) : 1339-1348, 2020-10

الإتاحة: https://doi.org/10.1080/14740338.2020.1792441Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/185010Test

المساهمون: College of Medicine, Dept. of Internal Medicine, Kyong Joo Lee, Jae Hee Cho, Sang Hyub Lee, Si Young Song, Kwang Hyuk Lee, Seok Jeong, Ji Kon Ryu, Sang Myung Woo, Seungmin Bang, Jong Kyun Lee, Tae Hoon Lee, Woo Hyun Paik, Yong Tae Kim, Woo Jin Lee, Bang, Seung Min, Song, Si Young

مصطلحات موضوعية: Adult, Aged, 80 and over, Anemia/chemically induced, Anemia/epidemiology, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, Disease-Free Survival, Everolimus/adverse effects, Everolimus/therapeutic use, Exanthema/chemically induced, Exanthema/epidemiology, Female, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local, Pancreatic Neoplasms/drug therapy, Pancreatic Neoplasms/pathology, Prognosis, Republic of Korea, Retrospective Studies, Stomatitis/chemically induced, Stomatitis/epidemiology, Treatment Outcome, Young Adult, Everolimus, Pancreatic neuroendocrine tumor

الوصف: PURPOSE: Everolimus is a standard treatment option for advanced pancreatic neuroendocrine tumors (pNETs). This multicenter study evaluated the efficacy and safety of everolimus in low and intermediate grade advanced pNETs. METHODS: Tumors were graded according to the World Health Organization 2010 classification system. Patients with low or intermediate grade pNETs who received everolimus as first- or second-line chemotherapy between 2002 and 2014 were included. RESULTS: A total of 40 patients with metastatic or recurrent pNETs were included in this study. The median age was 54.5 years (range 19-83 years). Twelve patients (30%) experienced recurrence. There were 11 patients (27.5%) with low grade pNETs and 29 (72.5%) with intermediate. Everolimus was administered as first-line therapy in 30 patients (75%) and as second-line therapy in 10 patients (25%). The median progression-free survival (PFS) of patients with low and intermediate grade pNETs was significantly different (median not reached vs. 11 months, P = 0.015). On multivariate analysis, tumor grade (intermediate grade; HR 6.52, 95% CI 1.31-32.27, P = 0.022) was the only independent prognostic factor for PFS in pNETs. The most common adverse events were stomatitis, skin rash, and anemia. CONCLUSIONS: World Health Organization 2010 grade is the most important determinant for PFS in patients undergoing everolimus treatment for pNETs with an acceptable incidence of adverse events. ; restriction

العلاقة: CANCER CHEMOTHERAPY AND PHARMACOLOGY; J00437; OAK-2017-05183; https://ir.ymlib.yonsei.ac.kr/handle/22282913/160894Test; https://link.springer.com/article/10.1007%2Fs00280-017-3421-7Test; T201703544; CANCER CHEMOTHERAPY AND PHARMACOLOGY, Vol.80(4) : 799-805, 2017

الإتاحة: https://doi.org/10.1007/s00280-017-3421-7Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160894Test

المساهمون: College of Medicine, Dept. of Internal Medicine, S. J. Kim, D.-Y. Shin, J. S. Kim, D. H. Yoon, W. S. Lee, H. Lee, Y. R. Do, H. J. Kang, H. S. Eom, Y. H. Ko, S. H. Lee, H. Y. Yoo, M. Hong, C. Suh, W. S. Kim, Kim, Jin Seok

مصطلحات موضوعية: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Cyclophosphamide/administration & dosage, Cyclophosphamide/adverse effects, Disease-Free Survival, Doxorubicin/administration & dosage, Doxorubicin/adverse effects, Drug Administration Schedule, Everolimus/administration & dosage, Everolimus/adverse effects, Female, Humans, Lymphoma, T-Cell, Peripheral/drug therapy, Peripheral/pathology, Male, Middle Aged, Neoplasm Staging, PTEN Phosphohydrolase/biosynthesis, PTEN Phosphohydrolase/genetics, Prednisone/administration & dosage, Prednisone/adverse effects, TOR Serine-Threonine Kinases/antagonists & inhibitors, TOR Serine-Threonine Kinases/genetics, Treatment Outcome, Vincristine/administration & dosage, Vincristine/adverse effects

الوصف: BACKGROUND: Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. PATIENTS AND METHODS: Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. RESULTS: The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. CONCLUSION: The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN. ; restriction

العلاقة: ANNALS OF ONCOLOGY; J00171; OAK-2016-07707; https://ir.ymlib.yonsei.ac.kr/handle/22282913/152779Test; T201605305; ANNALS OF ONCOLOGY, Vol.27(4) : 712-718, 2016

الإتاحة: https://doi.org/10.1093/annonc/mdv624Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152779Test

المؤلفون: Motzer, Robert, Alekseev, Boris, Rha, Sun-Young, Porta, Camillo, Eto, Masatoshi, Powles, Thomas, Grünwald, Viktor, Hutson, Thomas E, Kopyltsov, Evgeny, Méndez-Vidal, María J, Kozlov, Vadim, Alyasova, Anna, Hong, Sung-Hoo, Kapoor, Anil, Alonso Gordoa, Teresa, Merchan, Jaime R, Winquist, Eric, Maroto, Pablo, Goh, Jeffrey C, Kim, Miso, Gurney, Howard, Patel, Vijay, Peer, Avivit, Procopio, Giuseppe, Takagi, Toshio, Melichar, Bohuslav, Rolland, Frederic, De Giorgi, Ugo, Wong, Shirley, Bedke, Jens, Schmidinger, Manuela, Dutcus, Corina E, Smith, Alan D, Dutta, Lea, Mody, Kalgi, Perini, Rodolfo F, Xing, Dongyuan, Choueiri, Toni K, CLEAR Trial Investigators

المساهمون: Gennigens, Christine

المصدر: New England Journal of Medicine, 384 (14), 1289 - 1300 (2021-04-08)

مصطلحات موضوعية: Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Phenylurea Compounds, Programmed Cell Death 1 Receptor, Protein Kinase Inhibitors, Quinolines, Everolimus, pembrolizumab, lenvatinib, Sunitinib, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized/administration & dosage, Antibodies, Monoclonal, Humanized/adverse effects, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Carcinoma, Renal Cell/drug therapy, Carcinoma, Renal Cell/mortality, Everolimus/administration & dosage, Everolimus/adverse effects, Female, Humans, Kidney Neoplasms/drug therapy, Kidney Neoplasms/mortality, Male, Middle Aged, Phenylurea Compounds/administration & dosage, Phenylurea Compounds/adverse effects, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Progression-Free Survival, Protein Kinase Inhibitors/therapeutic use, Quinolines/administration & dosage, Quinolines/adverse effects, Sunitinib/adverse effects, Sunitinib/therapeutic use, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Kidney Neoplasms, Medicine (all), General Medicine, Human health sciences, Oncology, Sciences de la santé humaine, Oncologie

الوصف: [en] BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

العلاقة: http://www.nejm.org/doi/pdf/10.1056/NEJMoa2035716Test; urn:issn:0028-4793; urn:issn:1533-4406

الوصول الحر: https://orbi.uliege.be/handle/2268/300816Test

المؤلفون: Pozdzik, Agnieszka, Fernandez Vallone, Valeria, Demetter, Pieter, Tooulou, Monika, Matos Pinto De Almeida, Celso, Gammar, Nadia, Broeders, Emine Nilufer, Dratwa, Max, Nortier, Joëlle

المصدر: Peritoneal dialysis international, 35 (7

مصطلحات موضوعية: Néphrologie - urologie, Everolimus -- adverse effects, Female, Glomerulonephritis, Membranoproliferative -- surgery, Humans, Immunosuppressive Agents -- adverse effects, Kidney Transplantation -- adverse effects, Peritoneal Fibrosis -- diagnosis -- etiology -- therapy, Young Adult

الوصف: SCOPUS: no.j ; info:eu-repo/semantics/published

وصف الملف: 1 full-text file(s): application/pdf

العلاقة: uri/info:doi/10.3747/pdi.2014.00157; uri/info:pii/35/7/769; uri/info:pmid/26703854; uri/info:scp/84951288261; uri/info:pmcid/PMC4690640; https://dipot.ulb.ac.be/dspace/bitstream/2013/226649/3/PMC4690640.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/226649Test

الإتاحة: http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/226649Test
https://dipot.ulb.ac.be/dspace/bitstream/2013/226649/3/PMC4690640.pdfTest