• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Novel phase I trial design to evaluate the addition of cediranib or selumetinib to preoperative chemoradiotherapy for locally advanced rectal cancer: the DREAMtherapy trial

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Marti-Marti, Francisca
    Jayson, Gordon C
    Manoharan, Prakash
    O'Connor, James P B
    Renehan, Andrew G
    Backen, Alison C
    Mistry, H
    Ortega, F
    Li, K
    Simpson, Kathryn L
    Allen, J
    Connell, J
    Underhill, S
    Misra, Vivek
    Williams, Kaye J
    Stratford, I
    Jackson, Alan
    Dive, Caroline
    Saunders, Mark P
    Show allShow less
    Affiliation
    The Christie NHS Foundation Trust, Manchester, UK
    Issue Date
    2019
    
    Metadata
    Show full item record
    Abstract
    BACKGROUND: The DREAMtherapy (Dual REctal Angiogenesis MEK inhibition radiotherapy) trial is a novel intertwined design whereby two tyrosine kinase inhibitors (cediranib and selumetinib) were independently evaluated with rectal chemoradiotherapy (CRT) in an efficient manner to limit the extended follow-up period often required for radiotherapy studies. PATIENTS AND METHODS: Cediranib or selumetinib was commenced 10 days before and then continued with RT (45 Gy/25#/5 wks) and capecitabine (825 mg/m2 twice a day (BID)). When three patients in the cediranib 15-mg once daily (OD) cohort were in the surveillance period, recruitment to the selumetinib cohort commenced. This alternating schedule was followed throughout. Three cediranib (15, 20 and 30 mg OD) and two selumetinib cohorts (50 and 75 mg BID) were planned. Circulating and imaging biomarkers of inflammation/angiogenesis were evaluated. RESULTS: In case of cediranib, dose-limiting diarrhoea, fatigue and skin reactions were seen in the 30-mg OD cohort, and therefore, 20 mg OD was defined as the maximum tolerated dose. Forty-one percent patients achieved a clinical or pathological complete response (7/17), and 53% (9/17) had an excellent clinical or pathological response (ECPR). Significantly lower level of pre-treatment plasma tumour necrosis factor alpha (TNF?) was found in patients who had an ECPR. In case of selumetinib, the 50-mg BID cohort was poorly tolerated (fatigue and diarrhoea); a reduced dose cohort of 75-mg OD was opened which was also poorly tolerated, and further recruitment was abandoned. Of the 12 patients treated, two attained an ECPR (17%). CONCLUSIONS: This novel intertwined trial design is an effective way to independently investigate multiple agents with radiotherapy. The combination of cediranib with CRT was well tolerated with encouraging efficacy. TNF? emerged as a potential predictive biomarker of response and warrants further evaluation.
    Citation
    Marti FEM, Jayson GC, Manoharan P, O'Connor J, Renehan AG, Backen AC, et al. Novel phase I trial design to evaluate the addition of cediranib or selumetinib to preoperative chemoradiotherapy for locally advanced rectal cancer: the DREAMtherapy trial. Eur J Cancer. 2019 Jun 20;117:48-59.
    Journal
    European Journal of Cancer
    URI
    http://hdl.handle.net/10541/621922
    DOI
    10.1016/j.ejca.2019.04.029
    PubMed ID
    31229949
    Additional Links
    https://dx.doi.org/10.1016/j.ejca.2019.04.029
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2019.04.029
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • Phase I study of cediranib, an oral VEGFR inhibitor, in combination with selumetinib, an oral MEK inhibitor, in patients with advanced solid malignancies.
    • Authors: Hubbard JM, Yin J, Schenk EL, Qin R, Reid JM, Strand C, Fiskum J, Menefee M, Lin G, Doyle LA, Ivy P, Erlichman C, Adjei A, Haluska P, Costello BA
    • Issue date: 2022 Feb
    • Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study.
    • Authors: Czito BG, Deming DA, Jameson GS, Mulcahy MF, Vaghefi H, Dudley MW, Holen KD, DeLuca A, Mittapalli RK, Munasinghe W, He L, Zalcberg JR, Ngan SY, Komarnitsky P, Michael M
    • Issue date: 2017 Jun
    • Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis.
    • Authors: Takahashi O, Komaki R, Smith PD, Jürgensmeier JM, Ryan A, Bekele BN, Wistuba II, Jacoby JJ, Korshunova MV, Biernacka A, Erez B, Hosho K, Herbst RS, O'Reilly MS
    • Issue date: 2012 Mar 15
    • Phase I study of pre-operative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma.
    • Authors: Kim R, Prithviraj GK, Shridhar R, Hoffe SE, Jiang K, Zhao X, Chen DT, Almhanna K, Strosberg J, Campos T, Shibata D
    • Issue date: 2016 Feb
    • Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer: a dose-escalation study.
    • Authors: Caravatta L, Picardi V, Tambaro R, Padula GD, Macchia G, Deodato F, Massaccesi M, Pacelli F, Berardi S, Ridolfini MP, Di Filippo L, Fabrizio G, Ingrosso M, Cellini N, Valentini V, Morganti AG
    • Issue date: 2012 Oct
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.