دورية أكاديمية
Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399.
| العنوان: | Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399. |
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| المؤلفون: | Gentzler RD; Division of Hematology/Oncology, Department of Medicine, University of Virginia Cancer Center, Charlottesville, VA, USA., Villaruz LC; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Medical Center-Hillman Cancer Center, Pittsburgh, PA, USA., Rhee JC; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Medical Center-Hillman Cancer Center, Pittsburgh, PA, USA., Horton B; Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA., Mock J; Division of Hematology/Oncology, Department of Medicine, University of Virginia Cancer Center, Charlottesville, VA, USA., Hanley M; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA., Kim K; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Rudek MA; Department of Oncology and Medicine, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Phelps MA; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Carducci MA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Piekarz R; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA., Park KS; Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia Cancer Center, Charlottesville, VA, USA., Bullock TN; Department of Pathology, University of Virginia Cancer Center, Charlottesville, VA, USA., Rudin CM; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. |
| المصدر: | The oncologist [Oncologist] 2023 Nov 02; Vol. 28 (11), pp. 1007-e1107. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9607837 Publication Model: Print Cited Medium: Internet ISSN: 1549-490X (Electronic) Linking ISSN: 10837159 NLM ISO Abbreviation: Oncologist Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : Oxford : Oxford University Press Original Publication: Dayton, Ohio : AlphaMed Press, c1996- |
| مواضيع طبية MeSH: | Small Cell Lung Carcinoma*/drug therapy , Lung Neoplasms*/drug therapy , Neutropenia*/chemically induced , Thrombocytopenia*/chemically induced , Anemia*/chemically induced, Humans ; Male ; Female ; Etoposide ; Carboplatin ; Bayes Theorem ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use |
| مستخلص: | Background: CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors. Methods: Patients with treatment-naïve extensive-stage SCLC, ECOG ≤2 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%. Results: Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1: (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls. Conclusion: Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029). (© The Author(s) 2023. Published by Oxford University Press.) |
| References: | Clin Cancer Res. 2016 Aug 15;22(16):4119-32. (PMID: 26964571) Oncotarget. 2017 Dec 12;8(69):114156-114172. (PMID: 29371976) Cancer Discov. 2018 Nov;8(11):1422-1437. (PMID: 30181244) |
| معلومات مُعتمدة: | R01 CA273924 United States CA NCI NIH HHS; UM1 CA186690 United States CA NCI NIH HHS; 2UM1CA186691-06 and 2UM1CA186690-06 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; UM1 CA186691 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: atezolizumab; carboplatin; entinostat; etoposide; immunotherapy; small cell lung cancer |
| سلسلة جزيئية: | ClinicalTrials.gov NCT04631029 |
| المشرفين على المادة: | 6PLQ3CP4P3 (Etoposide) BG3F62OND5 (Carboplatin) 52CMI0WC3Y (atezolizumab) 1ZNY4FKK9H (entinostat) |
| تواريخ الأحداث: | Date Created: 20230809 Date Completed: 20231108 Latest Revision: 20240615 |
| رمز التحديث: | 20240615 |
| مُعرف محوري في PubMed: | PMC10628589 |
| DOI: | 10.1093/oncolo/oyad221 |
| PMID: | 37555284 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1549-490X |
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| DOI: | 10.1093/oncolo/oyad221 |