Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network.

Purpose: To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients.Methods: A population-based cohort study of new anti-VEGF users was conducted in two US healthcare databases, De...

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Publicado en:Cancer Chemotherapy & Pharmacology Vol. 78; no. 3; pp. 559 - 567
Autores principales: Shantakumar, Sumitra, Nordstrom, Beth, Djousse, Luc, Hall, Susan, Gagnon, David, Fraeman, Kathy, Herk-Sukel, Myrthe, Chagin, Karen, Nelson, Jeanenne, Nordstrom, Beth L, Hall, Susan A, Gagnon, David R, Fraeman, Kathy H, van Herk-Sukel, Myrthe
Formato: research Journal Article
Publicado: Springer Nature Sep2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Sep2016
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00280-016-3112-9
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        atl: Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network.
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        au:
          Shantakumar, Sumitra
          Nordstrom, Beth
          Djousse, Luc
          Hall, Susan
          Gagnon, David
          Fraeman, Kathy
          Herk-Sukel, Myrthe
          Chagin, Karen
          Nelson, Jeanenne
          Nordstrom, Beth L
          Hall, Susan A
          Gagnon, David R
          Fraeman, Kathy H
          van Herk-Sukel, Myrthe
        affil: Worldwide Epidemiology, R&D , GlaxoSmithKline , 150 Beach Road, #26-00 Gateway West Singapore 189720 Singapore
      sug:
        subj:
          Sulfonamides Therapeutic Use
          Kidney Neoplasms Drug Therapy
          Heterocyclic Compounds Therapeutic Use
          Antineoplastic Agents Therapeutic Use
          Carcinoma, Renal Cell Drug Therapy
          Heterocyclic Compounds Adverse Effects
          Sulfonamides Adverse Effects
          Carcinoma, Renal Cell Pathology
          Male
          Human
          Antineoplastic Agents Adverse Effects
          Urea Adverse Effects
          Middle Age
          Female
          Vascular Endothelial Growth Factor A Antagonists and Inhibitors
          Kidney Neoplasms Pathology
          Computer Communication Networks
          Prospective Studies
          Vitamin B Complex Adverse Effects
          Indoles Therapeutic Use
          Vitamin B Complex
          Aged
          Retrospective Design
          Urea Therapeutic Use
          Vitamin B Complex Therapeutic Use
          Indoles Adverse Effects
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Middle Aged: 45-64 years
          Aged: 65+ years
          Male
          Female
      ab: Purpose: To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients.Methods: A population-based cohort study of new anti-VEGF users was conducted in two US healthcare databases, Department of Veterans Affairs (VA) and an oncology practice network (Altos), and the PHARMO Database Network in The Netherlands. A common protocol was used to collect liver chemistry (LC) data from anti-VEGF initiation through 4 years of follow-up. In the VA population, suspected drug-induced liver injury (DILI) outcomes were investigated via chart review, with adjudication by hepatologists.Results: In Altos and VA, respectively, the total RCC patients were: pazopanib (156, 243), bevacizumab (122, 99), sorafenib (82, 249) and sunitinib (285, 751). PHARMO contained too few patients to be included. Few cases of alanine aminotransferase (ALT) ≥8× the upper limit of normal were seen across the anti-VEGF cohorts; incidence rates (per 100 person-years) ranged from 0 (sunitinib) to 8.2 (pazopanib) in Altos and from 0 (bevacizumab and sorafenib) to 2.1 (pazopanib) among VA patients. No cases of Hy's law identified by combination LC elevations were seen in patients treated with pazopanib or bevacizumab; one case was observed in those treated with sorafenib, and two cases were found among sunitinib users. One case of adjudicated DILI was observed in a sunitinib-treated patient; none were found among patients treated with pazopanib, bevacizumab or sorafenib.Conclusions: Severe liver injury occurred infrequently during exposure to pazopanib and other anti-VEGF therapies in a population-based setting.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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