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  1. Article ; Online: Correction: Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: a Phase I Dose Escalation and Expansion Study.

    Wang-Gillam, Andrea / Lim, Kian-Huat / McWilliams, Robert / Suresh, Rama / Lockhart, Albert C / Brown, Amberly / Breden, Marcus / Belle, Jad I / Herndon, John / Bogner, Savannah J / Pedersen, Katrina / Tan, Benjamin / Boice, Nicholas / Acharya, Abhi / Abdiannia, Mina / Gao, Feng / Yoon, Harry H / Zhu, Mojun / Trikalinos, Nikolaos A /
    Ratner, Lee / Aranha, Olivia / Hawkins, William G / Herzog, Brett H / DeNardo, David G

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2023  Volume 29, Issue 22, Page(s) 4698

    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-2993
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Phase 1 study combining alisertib with nab-paclitaxel in patients with advanced solid malignancies.

    Lim, Kian-Huat / Opyrchal, Mateusz / Acharya, Abhi / Boice, Nick / Wu, Ningying / Gao, Feng / Webster, Jace / Lockhart, Albert C / Waqar, Saiama N / Govindan, Ramaswamy / Morgensztern, Daniel / Picus, Joel / Tan, Benjamin R / Baggstrom, Maria Q / Maher, Christopher A / Wang-Gillam, Andrea

    European journal of cancer (Oxford, England : 1990)

    2021  Volume 154, Page(s) 102–110

    Abstract: Aim: Aurora kinase A (AURKA) is a pleiotropic serine/threonine kinase that orchestrates mitotic progression. Paclitaxel stabilises microtubules and disrupts mitotic spindle assembly. The combination of AURKA inhibitor (alisertib) plus paclitaxel may be ... ...

    Abstract Aim: Aurora kinase A (AURKA) is a pleiotropic serine/threonine kinase that orchestrates mitotic progression. Paclitaxel stabilises microtubules and disrupts mitotic spindle assembly. The combination of AURKA inhibitor (alisertib) plus paclitaxel may be synergistic in rapidly proliferative cancers. We evaluated the safety and maximum tolerated dose (MTD) of alisertib in combination with nab-paclitaxel and its preliminary efficacy in patients with refractory high-grade neuroendocrine tumours (NETs).
    Method: This is a two-part, Phase 1 study. In Part A (dose escalation), a standard 3 + 3 design was used to determine MTD. In Part B (dose expansion), patients with predominantly refractory high-grade NETs were enrolled.
    Results: In total, 31 patients were enrolled and treated (16 in Part A and 15 in Part B). The MTD of alisertib was 40 mg BID on D1-3 per week and nab-paclitaxel 100mg/m
    Conclusions: The combination of alisertib and nab-paclitaxel has manageable side-effect profile and showed promising preliminary efficacy in high-grade NETs, warranting further testing.
    Trial registration: ClinicalTrials.gov identifier: NCT01677559.
    MeSH term(s) Adult ; Aged ; Albumins/administration & dosage ; Albumins/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Azepines/administration & dosage ; Azepines/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors/drug therapy ; Neuroendocrine Tumors/mortality ; Paclitaxel/administration & dosage ; Paclitaxel/adverse effects ; Pyrimidines/administration & dosage ; Pyrimidines/adverse effects
    Chemical Substances 130-nm albumin-bound paclitaxel ; Albumins ; Azepines ; MLN 8237 ; Pyrimidines ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2021-07-10
    Publishing country England
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 82061-1
    ISSN 1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
    ISSN (online) 1879-0852
    ISSN 0277-5379 ; 0959-8049 ; 0964-1947
    DOI 10.1016/j.ejca.2021.06.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 456: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 583: Show issues

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  3. Article ; Online: Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study.

    Wang-Gillam, Andrea / Lim, Kian-Huat / McWilliams, Robert / Suresh, Rama / Lockhart, Albert C / Brown, Amberly / Breden, Marcus / Belle, Jad I / Herndon, John / Bogner, Savannah J / Pedersen, Katrina / Tan, Benjamin / Boice, Nicholas / Acharya, Abhi / Abdiannia, Mina / Gao, Feng / Yoon, Harry H / Zhu, Mojun / Trikalinos, Nikolaos A /
    Ratner, Lee / Aranha, Olivia / Hawkins, William G / Herzog, Brett H / DeNardo, David G

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2022  Volume 28, Issue 24, Page(s) 5254–5262

    Abstract: Purpose: Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.: Patients and ... ...

    Abstract Purpose: Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.
    Patients and methods: We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity.
    Results: The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively.
    Conclusions: The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
    MeSH term(s) Animals ; Mice ; Gemcitabine ; Deoxycytidine ; Albumins ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Pancreatic Neoplasms/pathology ; Adenocarcinoma/pathology ; Pancreatic Neoplasms
    Chemical Substances Gemcitabine ; defactinib (53O87HA2QU) ; Deoxycytidine (0W860991D6) ; pembrolizumab (DPT0O3T46P) ; Albumins ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2022-10-14
    Publishing country United States
    Document type Clinical Trial, Phase I ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-22-0308
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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