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MeSH: cisplatina-škodlivé účinky

47 záznamů v PubMed Filtry

Článek

Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer

Powles, Thomas
Autor Powles, Thomas From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Catto, James W F
Autor Catto, James W F ORCID From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Galsky, Matthew D
Autor Galsky, Matthew D From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Al-Ahmadie, Hikmat
Autor Al-Ahmadie, Hikmat ORCID From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Meeks, Joshua J
Autor Meeks, Joshua J From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Nishiyama, Hiroyuki
Autor Nishiyama, Hiroyuki From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Vu, Toan Quang
Autor Vu, Toan Quang From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Antonuzzo, Lorenzo
Autor Antonuzzo, Lorenzo From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Wiechno, Pawel
Autor Wiechno, Pawel From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)
Atduev, Vagif
Autor Atduev, Vagif From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.)

The New England journal of medicine. 2024 Nov 14 ; 391 (19) : 1773-1786. [epub] 20240915

N Engl J Med
ISSN 1533-4406 | 0028-4793
Zdroj

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. METHODS: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. RESULTS: In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. CONCLUSIONS: Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.).

Článek

First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study

Cancer research communications. 2024 Jun 28 ; 4 (6) : 1609-1619.

Cancer Res Commun
ISSN 2767-9764
Zdroj

PURPOSE: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase Ib) and confirmed objective response (phase Ib/II). RESULTS: In phase Ib, urothelial carcinoma and NSCLC cohorts received avelumab 800 mg (n = 13 and n = 6, respectively) or 1,200 mg (n = 6 each) + chemotherapy. In evaluable patients with urothelial carcinoma treated with avelumab 800 or 1,200 mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT occurred in the NSCLC cohort. In phase II, 35 additional patients with urothelial carcinoma received avelumab 1,200 mg + chemotherapy. Across all treated patients, safety profiles were similar irrespective of avelumab dose. Objective response rates (95% confidence internal) with avelumab 800 or 1,200 mg + chemotherapy, respectively, across phase Ib/II, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0% (11.8-88.2) and 33.3% (4.3-77.7) in NSCLC. CONCLUSIONS: Preliminary efficacy and safety findings with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with previous studies of similar combination regimens. Conclusions about clinical activity are limited by small patient numbers. SIGNIFICANCE: This phase Ib/II trial evaluated avelumab (immune checkpoint inhibitor) administered concurrently with standard first-line chemotherapy in patients with advanced urothelial carcinoma or advanced nonsquamous NSCLC without actionable mutations. Efficacy and safety appeared consistent with previous studies of similar combinations, although patient numbers were small.

Článek

Determination of Renal Distribution of Zinc, Copper, Iron, and Platinum in Mouse Kidney Using LA-ICP-MS

BioMed research international. 2021 ; 2021 () : 6800294. [epub] 20211026

Biomed Res Int
ISSN 2314-6141
Zdroj

The main dose-limiting side effect of cisplatin is nephrotoxicity. The utilization of cisplatin is an issue of balancing tumour toxicity versus platinum-induced nephrotoxicity. In this study, we focused on intraorgan distribution of common essential trace elements zinc, copper, and iron in healthy mouse kidneys and distribution of platinum after cisplatin treatment. Renal distribution in 12 nontreated Nu-Nu mice (males) was assessed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Furthermore, 9 Nu-Nu mice were treated with cisplatin. The order of elements concentration in kidneys was as follows: Fe > Zn > Cu. All three metals showed the higher concentrations at the cortex and medulla (28.60, 3.35, and 93.83 μg/g for Zn, Cu, and Fe, respectively) and lower concentration at the pelvis and the urinary tract (20.20, 1.93, and 62.48 μg/g for Zn, Cu, and Fe, respectively). No statistically significant difference between cortex and medulla was observed for these elements. After platinum treatment, the concentration of platinum in kidneys was enhanced more than 60-times, p < 0.001. Platinum significantly showed the highest accumulation in cortex (2.11 μg/g) with a gradient distribution. Platinum was less accumulated in medulla and pelvis than in cortex, and the lowest accumulation occurred in the urinary tract (1.13 μg/g). Image processing has been successfully utilized to colocalize metal distribution using LA-ICP-MS and histological samples images.

MeSH
buňky PC-3 MeSH
cisplatina škodlivé účinky farmakologie toxicita MeSH
hmotnostní spektrometrie metody MeSH
ledviny účinky léků metabolismus patologie MeSH
lidé MeSH
měď analýza MeSH
myši nahé MeSH
myši MeSH
platina analýza MeSH
spektrální analýza metody MeSH
železo analýza MeSH
zinek analýza MeSH
zvířata MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
Názvy látek
cisplatina MeSH
měď MeSH
platina MeSH
železo MeSH
zinek MeSH

Článek

Pathological response and clinical outcomes in operable triple-negative breast cancer with cisplatin added to standard neoadjuvant chemotherapy

Klinicka onkologie. 2021 Winter ; 34 (1) : 49-55.

Klin Onkol
ISSN 1802-5307 | 0862-495X
Zdroj

BACKGROUND: Response to neoadjuvant chemotherapy is associated with improved outcomes for patients with triple negative breast cancer (TNBC). Patients with residual disease are at increased risk of relapse and death from breast cancer. In this retrospective study, we aimed to evaluate the efficacy and safety of cisplatin added to standard neoadjuvant chemotherapy for locally advanced TNBC. MATERIALS AND METHODS: All TNBC treated with neoadjuvant cisplatin 60mg/m2 once in 3 weeks with weekly paclitaxel for 12 weeks, following 8 weeks of dose-dense epirubicin 90mg/m2 or doxorubicin 60mg/m2 with cyclophosphamide 600mg/m2 were analyzed retrospectively. The data related to pathological complete response, adherence to planned therapy, disease-free survival and overall survival were collected. RESULTS: Eighty-three patients were included, of whom 80% had stage III disease. Pathological complete response in both breast (T0/Tis) and axilla (N0) was observed in 48.1% of patients. Miller Payne grade 5 pathological response in the breast was seen in 61% of patients. Good partial responses (Miller Payne grades 3,4) were observed in 32.5% of patients. The remaining 6.5% were poor responders. Seventy-seven patients underwent surgery. The disease-free survival at 1 and 3 years for those who had a pathological complete response was 96.7% and 77.6%, respectively, and 92.3% and 62.7% for those who did not, respectively. The predominant adverse events were hematological, with anemia being the most common one. CONCLUSION: The addition of cisplatin to neoadjuvant chemotherapy with anthracycline and taxane in TNBC was tolerable and produced a high rate of pathological complete response. Cisplatin added to standard chemotherapy in patients with locally advanced TNBC could improve clinical outcomes.

Klíčová slova
cisplatin, neoadjuvant chemotherapy, pathological complete response, residual cancer burden, triple negative breast cancer,
MeSH
anemie chemicky indukované MeSH
cisplatina aplikace a dávkování škodlivé účinky MeSH
cyklofosfamid aplikace a dávkování škodlivé účinky MeSH
dospělí MeSH
doxorubicin aplikace a dávkování škodlivé účinky MeSH
epirubicin aplikace a dávkování škodlivé účinky MeSH
kombinovaná farmakoterapie MeSH
lidé středního věku MeSH
lidé MeSH
mladý dospělý MeSH
neoadjuvantní terapie MeSH
paclitaxel aplikace a dávkování škodlivé účinky MeSH
protinádorové látky aplikace a dávkování škodlivé účinky MeSH
retrospektivní studie MeSH
staging nádorů MeSH
triple-negativní karcinom prsu farmakoterapie patologie chirurgie MeSH
výsledek terapie MeSH
Check Tag
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
mladý dospělý MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
Názvy látek
cisplatina MeSH
cyklofosfamid MeSH
doxorubicin MeSH
epirubicin MeSH
paclitaxel MeSH
protinádorové látky MeSH

Článek

The use of cisplatin in patients after kidney transplantation with chronic renal insufficiency: Is the benefit higher than potential risks in therapy of non-seminomatous germ cell tumors?

Medicine. 2021 Jun 18 ; 100 (24) : e26381.

Medicine (Baltimore)
ISSN 1536-5964 | 0025-7974
Zdroj

RATIONALE: The use of cisplatin in patients with chronic kidney disease (CKD) is risky and depends on a number of factors. The optimal procedure in stage I of a non seminomatous germ cell tumor without proven lymphangioinvasion after orchiectomy is controversial and is the subject of a number of discussions due to the lack of randomized studies assessing individual treatment options. The adjuvant method of choice is surveillance or application of cisplatin-based chemotherapy with the risk of treatment related nephrotoxicity. Information about cisplatin safety in renal transplant patients is particularly limited. The aim of this paper is to share the experience with the application of adjuvant chemotherapy Bleomycin, Etoposide, Cisplatin (BEP) in high-risk patient with nonseminoma after kidney transplantation. PATIENT CONCERNS: We report a case report of rare group of high-risk patient with non-seminomatous germ cell testicular tumor (NSGCT) after kidney transplantation before application of adjuvant chemotherapy BEP. Patient presented with month-long discomfort in the scrotal area. Previously, he was treated with chronic kidney disease based on chronic glomerulonephritis, which was treated with repeated kidney transplantation. DIAGNOSIS: The ultrasound examination for a month-long discomfort in the scrotal area found a solid mass of the left testis. Radical inguinal orchiectomy confirmed NSGCT with the presence of lymphovascular invasion (LVI). Postoperative staging with computed tomography of the chest and abdomen did not show obvious dissemination of the disease. INTERVENTIONS: Reducing original dose of chemotherapeutics according to the recommendations of the summary of product characteristics led to only a transient increase in creatinine levels. OUTCOMES: The 5-year risk of relapse in surveillance was reduced to around 3% by applying cisplatin-based chemotherapy. LESSONS: Application of cisplatin-based chemotherapy is safe and effective in patients with CKD and in patients with a kidney transplant.

MeSH
adjuvantní chemoterapie MeSH
bleomycin škodlivé účinky terapeutické užití MeSH
chronická renální insuficience komplikace imunologie chirurgie MeSH
cisplatina škodlivé účinky terapeutické užití MeSH
etoposid škodlivé účinky terapeutické užití MeSH
germinální a embryonální nádory komplikace farmakoterapie chirurgie MeSH
hodnocení rizik MeSH
lidé středního věku MeSH
lidé MeSH
orchiektomie MeSH
protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
testikulární nádory komplikace farmakoterapie chirurgie MeSH
transplantace ledvin * MeSH
Check Tag
lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
Publikační typ
časopisecké články MeSH
kazuistiky MeSH
Názvy látek
bleomycin MeSH
cisplatina MeSH
etoposid MeSH

Článek

Adverse events of different chemotherapy regimens in the first-line treatment of patients with advanced or metastatic urothelial cancer: A systematic review and network meta-analysis of randomized controlled trials

Seminars in oncology. 2021 Jun ; 48 (3) : 181-192. [epub] 20211002

Semin Oncol
ISSN 1532-8708 | 0093-7754
Zdroj

INTRODUCTION: The present systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used chemotherapy regimens for first-line therapy of advanced or metastatic urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The MEDLINE and EMBASE databases were searched for articles published between January 2000 and June 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis extension statement for NMA. Eligible studies included RCTs comparing different first-line chemotherapy regimens for treating advanced or metastatic UCB and AEs as outcome measures. A NMA was performed to assess the mortality rates related to AEs and discontinuation of treatment due to toxicity as well as all AEs. RESULTS: Fourteen trials comprising 2,615 patients met our eligibility criteria and formal NMAs were conducted. Results revealed that gemcitabine plus carboplatin had the lowest likelihood of mortality related to AEs (P score: 0.8079), while larotaxel plus cisplatin and paclitaxel, cisplatin plus gemcitabine had both a lower toxicity rate leading to discontinuation (P score: 0.7295 and P score: 0.7242, respectively). Compared with gemcitabine plus cisplatin (GC), most chemotherapy regimens were associated with a lower likelihood of thrombocytopenia, anemia, and cardiovascular toxicity. In contrast, most chemotherapy regimens compared with GC were associated with a higher likelihood of neutropenia, central (fatigue, neuropathy) and gastrointestinal AEs, infections, as well as renal and pulmonary toxicities. CONCLUSION: Results of the present study demonstrated that hematological toxicity was the most prevalent AE associated with gemcitabine-containing regimens, while central AEs and febrile neutropenia were more commonly in taxane-containing regimens. GC had the lowest rate of gastrointestinal AEs, infection disorders, and pulmonary toxicities. Cisplatin-containing regimens were associated with a higher rate of renal and cardiovascular toxicity. These differential AEs may help in the detection of the personalized therapy in addition of efficacy data.

Klíčová slova
Adverse events, Chemotherapy, First-line, Network meta-analyses, RCT, UCB, Urothelial cancer,
MeSH
cisplatina škodlivé účinky MeSH
karcinom z přechodných buněk * farmakoterapie MeSH
lidé MeSH
nádory močového měchýře * farmakoterapie MeSH
protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
randomizované kontrolované studie jako téma MeSH
síťová metaanalýza MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
metaanalýza MeSH
práce podpořená grantem MeSH
přehledy MeSH
systematický přehled MeSH
Názvy látek
cisplatina MeSH

Článek

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial

The Lancet. Oncology. 2021 Jan ; 22 (1) : 51-65. [epub] 20201204

Lancet Oncol
ISSN 1474-5488 | 1470-2045
Zdroj

BACKGROUND: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone. METHODS: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum-etoposide, durvalumab plus platinum-etoposide, or platinum-etoposide alone. In all groups, patients received etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL/min or cisplatin 75-80 mg/m2 on day 1 of each cycle. Patients in the platinum-etoposide group received up to six cycles of platinum-etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum-etoposide versus platinum-etoposide and for durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. FINDINGS: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum-etoposide, 268 to durvalumab plus platinum-etoposide, and 269 to platinum-etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3-27·9). Durvalumab plus tremelimumab plus platinum-etoposide was not associated with a significant improvement in overall survival versus platinum-etoposide (hazard ratio [HR] 0·82 [95% CI 0·68-1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6-12·0) versus 10·5 months (9·3-11·2). Durvalumab plus platinum-etoposide showed sustained improvement in overall survival versus platinum-etoposide (HR 0·75 [95% CI 0·62-0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3-14·7) versus 10·5 months (9·3-11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum-etoposide group, and 88 [33%] of 266 patients in the platinum-etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 85 (32%) in the durvalumab plus platinum-etoposide group, and 97 (36%) in the platinum-etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum-etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum-etoposide group (pancytopenia and thrombocytopenia [n=1 each]). INTERPRETATION: First-line durvalumab plus platinum-etoposide showed sustained overall survival improvement versus platinum-etoposide but the addition of tremelimumab to durvalumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. These results support the use of durvalumab plus platinum-etoposide as a new standard of care for the first-line treatment of ES-SCLC. FUNDING: AstraZeneca.

Článek

Older age is a protective factor for academic achievements irrespective of treatment modalities for posterior fossa brain tumours in children

PloS one. 2020 ; 15 (12) : e0243998. [epub] 20201216

PLoS One
ISSN 1932-6203
Zdroj

The treatment of children with posterior fossa brain tumours (PFBT) impacts their long term functional and imaging outcomes. This study aimed to evaluate academic achievement correlated with long-term sequelae after different PFBT treatment modalities. The study cohort consisted of 110 survivors (median age at diagnosis 10.1 years and median time of follow up 13.2 years) who completed hearing questionnaires, neurological assessment and MRI of the brain ≥5 years after the end of treatment. There were three treatment groups. A cisplatin group which underwent cisplatin chemotherapy, radiotherapy and surgery (medulloblastoma N = 40), a radiotherapy group which underwent radiotherapy and surgery (astrocytoma/ependymoma N = 30), and a surgery group (astrocytoma N = 40). Academic achievement was correlated to the age at diagnosis, ototoxicity, Karnofsky score (KS), and MRI findings (Fazekas Score (FS)- treatment related parenchymal changes). For a modelled age at diagnosis of five years, the cisplatin group had lower academic achievements compared to the radiotherapy (p = 0.028) and surgery (p = 0.014) groups. Academic achievements evaluated at a modelled age of 10 years at diagnosis did not significantly differ among the treatment groups. The cisplatin group exhibited a higher occurrence of ototoxicity than the radiotherapy (p<0.019) and surgery groups (p<0.001); however, there was no correlation between ototoxicity and academic achievements (p = 0.722) in older age at diagnosis. The radiotherapy group exhibited lower KS than the surgery group (p<0.001). KS significantly influenced academic achievements in all groups (p<0.000). The cisplatin group exhibited higher FS than the surgery group (p<0.001) while FS did not correlate with academic achievement (p = 0.399). Older age is a protective factor for academic achievements irrespective of a treatment modality.

MeSH
cisplatina škodlivé účinky terapeutické užití MeSH
dítě MeSH
gliom epidemiologie chirurgie terapie MeSH
infratentoriální nádory epidemiologie chirurgie terapie MeSH
lidé MeSH
mladiství MeSH
neurochirurgické výkony škodlivé účinky MeSH
přežívající onkologičtí pacienti výchova MeSH
protinádorové látky škodlivé účinky MeSH
radioterapie škodlivé účinky MeSH
školní úspěšnost * MeSH
věkové faktory MeSH
Check Tag
dítě MeSH
lidé MeSH
mladiství MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
cisplatina MeSH
protinádorové látky MeSH

Článek

Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the European PanCareLIFE cohort study

European journal of cancer (Oxford, England. 2020 Oct ; 138 () : 212-224. [epub] 20200906

Eur J Cancer
ISSN 1879-0852 | 0959-8049
Zdroj

BACKGROUND: Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic markers. METHODS: Eligibility criteria required patients to be aged less than 19 years at the start of chemotherapy, which had to include cisplatin and/or carboplatin. Patients were assigned to three phenotype categories: no, minor and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1 and ACYP2) were investigated. Multinomial logistic regression was performed to model the relationship between genetic predictors and platinum ototoxicity, adjusting for clinical risk factors. Additionally, measures of the diagnostic accuracy of the genetic markers were determined. RESULTS: 900 patients were included in this study. In the multinomial logistic regression, significant unique contributions were found from SLC22A2 rs316019, the age at the start of platinum treatment, cranial radiation and the interaction term [platinum compound]∗[cumulative dose of cisplatin]. The predictive performance of the genetic markers was poor compared with the clinical risk factors. CONCLUSIONS: PanCareLIFE is the largest study of cisplatin-induced ototoxicity to date and confirmed a role for the polyspecific organic cation transporter SLC22A2. However, the predictive value of the current genetic candidate markers for clinical use is negligible, which puts the value of clinical factors for risk assessment of cisplatin-induced ototoxicity back into the foreground.

Klíčová slova
Adverse drug reaction, Anti-neoplastic drugs, Cancer survivors, Childhood cancer, Cisplatin: carboplatin, Drug-induced ototoxicity, Genetic markers, Multicenter cohort study, Pharmacogenetics,
MeSH
cisplatina škodlivé účinky MeSH
dítě MeSH
farmakogenomické testování MeSH
farmakogenomické varianty * MeSH
genetická predispozice k nemoci MeSH
genetické asociační studie MeSH
hodnocení rizik MeSH
jednonukleotidový polymorfismus * MeSH
karboplatina škodlivé účinky MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
nádory farmakoterapie MeSH
novorozenec MeSH
ototoxicita MeSH
percepční nedoslýchavost chemicky indukované genetika patofyziologie MeSH
předškolní dítě MeSH
přežívající onkologičtí pacienti * MeSH
prospektivní studie MeSH
protinádorové látky škodlivé účinky MeSH
průřezové studie MeSH
retrospektivní studie MeSH
rizikové faktory MeSH
sluch účinky léků MeSH
transportér organických kationtů 2 genetika MeSH
věk při počátku nemoci MeSH
Check Tag
dítě MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
mužské pohlaví MeSH
novorozenec MeSH
předškolní dítě MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
multicentrická studie MeSH
práce podpořená grantem MeSH
Geografické názvy
Evropa MeSH
Názvy látek
cisplatina MeSH
karboplatina MeSH
protinádorové látky MeSH
SLC22A2 protein, human MeSH Prohlížeč
transportér organických kationtů 2 MeSH

Článek

Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study

The pharmacogenomics journal. 2020 Apr ; 20 (2) : 294-305. [epub] 20191031

Pharmacogenomics J
ISSN 1473-1150 | 1470-269X
Zdroj

Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8-21.5; P = 5.6 × 10-7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3-4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04-14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07-2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

MeSH
cisplatina škodlivé účinky MeSH
dítě MeSH
genetická variace genetika MeSH
genetické asociační studie metody MeSH
internacionalita * MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
mladý dospělý MeSH
nádory farmakoterapie epidemiologie genetika MeSH
nedoslýchavost chemicky indukované epidemiologie genetika MeSH
novorozenec MeSH
ototoxicita epidemiologie genetika MeSH
předškolní dítě MeSH
protinádorové látky škodlivé účinky MeSH
retrospektivní studie MeSH
Check Tag
dítě MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
mladý dospělý MeSH
mužské pohlaví MeSH
novorozenec MeSH
předškolní dítě MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
multicentrická studie MeSH
práce podpořená grantem MeSH
Názvy látek
cisplatina MeSH
protinádorové látky MeSH

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