Natale, R., Blackhall, F., Kowalski, D. et al. (14 more authors) (2014) Evaluation of Antitumor Activity Using Change in Tumor Size of the Survivin Antisense Oligonucleotide LY2181308 in Combination with Docetaxel for Second-Line Treatment of Patients with Non-Small-Cell Lung Cancer A Randomized Open-Label Phase II Study. Journal of Thoracic Oncology, 9 (11). pp. 1704-1708. ISSN 1556-0864
Abstract
Chemoresistance is mediated, in part, by the inhibition of apoptosis in tumor cells. Survivin is an antiapoptotic protein that blocks chemotherapy-induced apoptosis. To investigate whether blocking survivin expression enhances docetaxel-induced apoptosis in patients with non–small-cell lung cancer (NSCLC), we compared the antitumor activity of the survivin inhibitor LY2181308 plus docetaxel with docetaxel alone. We used change in tumor size (CTS) as a primary endpoint to assess its use in early decision-making for this and future studies of novel agents in NSCLC. Patients (N = 162) eligible for second-line NSCLC treatment (stage IIIB/IV) with an Eastern Cooperative Oncology Group performance status of 0 to 1 were randomized 2:1 to receive LY2181308 (750 mg intravenously, weekly) and docetaxel (75 mg/m2 intravenously, day 1) or docetaxel alone every 21 days. CTS from baseline to the end of cycle 2 was compared between the two treatment arms. The mean (SD) tumor size ratio for LY2181308/docetaxel and docetaxel was 1.05 (0.21) and 1.00 (0.15) (p = 0.200), respectively, suggesting no significant improvement in antitumor activity between the arms. Because there was also no significant difference between the two arms for progression-free survival (PFS) (2.83 months with LY2181308/docetaxel and 3.35 months with docetaxel [p = 0.191]), both arms were combined. Using the combined arms, CTS correlated with PFS (PFS = 4.63 months in patients with decreased CTS compared with 2.66 months in patients with increased CTS), supporting its use in early decision-making in phase II studies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Elsevier. This is an author produced version of a paper subsequently published in Journal of Thoracic Oncology. Uploaded in accordance with the publisher's self-archiving policy. Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | Change in tumor size; Non-small-cell lung cancer; Docetaxel; Survivin; LY2181308 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Feb 2017 10:46 |
Last Modified: | 09 Feb 2017 10:46 |
Published Version: | https://doi.org/10.1097/JTO.0000000000000285 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1097/JTO.0000000000000285 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110808 |