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.
Blackhall, Fiona H
Summers, Yvonne J
AffiliationCedars-Sinai Medical Center, Los Angeles, California
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AbstractChemoresistance 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/m 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.
CitationEvaluation 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 2014, 9 (11):1704-8 J Thorac Oncol
JournalJournal of Thoracic Oncology
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- Authors: Auliac JB, Chouaid C, Greillier L, Monnet I, Le Caer H, Falchero L, Corre R, Descourt R, Bota S, Berard H, Schott R, Bizieux A, Fournel P, Labrunie A, Marin B, Vergnenegre A, GFPC team.
- Issue date: 2014 Sep
- Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer.
- Authors: Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pesek M, Spásová I, Belani CP, Bodrogi I, Gadgeel S, Kennedy SJ, Hou J, Herbst RS
- Issue date: 2007 Sep 20
- Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial.
- Authors: Shukuya T, Yamanaka T, Seto T, Daga H, Goto K, Saka H, Sugawara S, Takahashi T, Yokota S, Kaneda H, Kawaguchi T, Nagase S, Oguri T, Iwamoto Y, Nishimura T, Hattori Y, Nakagawa K, Nakanishi Y, Yamamoto N, West Japan Oncology Group.
- Issue date: 2015 Dec
- Double-blind, placebo-controlled, randomized phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer.
- Authors: Ready N, Karaseva NA, Orlov SV, Luft AV, Popovych O, Holmlund JT, Wood BA, Leopold L
- Issue date: 2011 Apr
- Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology.
- Authors: Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R, Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P, Johnson C, Breen T, White A, Einhorn L, Hoosier Oncology Group., US Oncology.
- Issue date: 2008 Dec 10