دورية أكاديمية
أعرض في EDS

Dual Src and EGFR inhibition in combination with gemcitabine in advanced pancreatic cancer: phase I results : A phase I clinical trial.

التفاصيل البيبلوغرافية
العنوان: Dual Src and EGFR inhibition in combination with gemcitabine in advanced pancreatic cancer: phase I results : A phase I clinical trial.
المؤلفون: Cardin DB; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. dana.cardin@vanderbilt.edu.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. dana.cardin@vanderbilt.edu., Goff LW; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Chan E; Amgen Inc., Thousand Oaks, CA, USA., Whisenant JG; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Dan Ayers G; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA., Takebe N; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA., Arlinghaus LR; Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA., Yankeelov TE; Institute for Computational and Engineering Sciences, Departments of Biomedical Engineering and Diagnostic Medicine, Livestrong Cancer Institutes, University of Texas, Austin, TX, USA., Berlin J; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Merchant N; Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
المصدر: Investigational new drugs [Invest New Drugs] 2018 Jun; Vol. 36 (3), pp. 442-450. Date of Electronic Publication: 2017 Oct 09.
نوع المنشور: Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 8309330 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-0646 (Electronic) Linking ISSN: 01676997 NLM ISO Abbreviation: Invest New Drugs Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Springer
Original Publication: Boston : M. Nijhoff, 1983-
مواضيع طبية MeSH: Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Deoxycytidine/*analogs & derivatives , Pancreatic Neoplasms/*drug therapy , Protein Kinase Inhibitors/*therapeutic use , src-Family Kinases/*antagonists & inhibitors, Aged ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; CA-19-9 Antigen/metabolism ; Deoxycytidine/adverse effects ; Deoxycytidine/therapeutic use ; Diffusion Magnetic Resonance Imaging ; ErbB Receptors/antagonists & inhibitors ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/diagnostic imaging ; Protein Kinase Inhibitors/adverse effects ; Gemcitabine
مستخلص: Pancreatic adenocarcinoma remains a major therapeutic challenge, as the poor (<8%) 5-year survival rate has not improved over the last three decades. Our previous preclinical data showed cooperative attenuation of pancreatic tumor growth when dasatinib (Src inhibitor) was added to erlotinib (EGFR inhibitor) and gemcitabine. Thus, this study was designed to determine the maximum-tolerated dose of the triplet combination. Standard 3 + 3 dose escalation was used, starting with daily oral doses of 70 mg dasatinib and 100 mg erlotinib with gemcitabine on days 1, 8, and 15 (800 mg/m 2 ) of a 28-day cycle (L 0 ). Nineteen patients were enrolled, yet 18 evaluable for dose-limiting toxicities (DLTs). One DLT observed at L 0 , however dasatinib was reduced to 50 mg (L -1 ) given side effects observed in the first two patients. At L -1 , a DLT occurred in 1/6 patients and dose was re-escalated to L 0 , where zero DLTs reported in next four patients. Dasatinib was escalated to 100 mg (L 1 ) where 1/6 patients experienced a DLT. Although L 1 was tolerable, dose escalation was stopped as investigators felt L 1 was within the optimal therapeutic window. Most frequent toxicities were anemia (89%), elevated aspartate aminotransferase (79%), fatigue (79%), nausea (79%), elevated alanine aminotransferase (74%), lymphopenia (74%), leukopenia (74%), neutropenia (63%), and thrombocytopenia (63%), most Grade 1/2. Stable disease as best response was observed in 69% (9/13). Median progression-free and overall survival was 3.6 and 8 months, respectively. Dasatinib, erlotinib, and gemcitabine was safe with manageable side effects, and with encouraging preliminary clinical activity in advanced pancreatic cancer.
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معلومات مُعتمدة: L30 CA162282 United States CA NCI NIH HHS; P30 CA068485 United States CA NCI NIH HHS; 9043 International Clinical Trials Evaluation Program; UM1 CA186689 United States CA NCI NIH HHS; U01 CA142565 United States CA NCI NIH HHS; R01 CA161976 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Dasatinib; Dual Src and EGFR inhibition; Erlotinib; Pancreatic cancer
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (CA-19-9 Antigen)
0 (Protein Kinase Inhibitors)
0W860991D6 (Deoxycytidine)
EC 2.7.10.1 (EGFR protein, human)
EC 2.7.10.1 (ErbB Receptors)
EC 2.7.10.2 (src-Family Kinases)
0 (Gemcitabine)
تواريخ الأحداث: Date Created: 20171010 Date Completed: 20190225 Latest Revision: 20230210
رمز التحديث: 20230210
مُعرف محوري في PubMed: PMC5891394
DOI: 10.1007/s10637-017-0519-z
PMID: 28990119
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-0646
DOI:10.1007/s10637-017-0519-z