A phase i trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours

European Journal of Cancer

Volumn 50, Issue 5, 2014, Pages 867-875

  Tolcher, Anthony ^a   Goldman, Jonathan ^b   Patnaik, Amita ^a   Papadopoulos, Kyriakos P ^a   Westwood, Paul ^c   Kelly, Claudia S ^c   Bumgardner, William ^c   Sams, Lillian ^c   Geeganage, Sandaruwan ^c   Wang, Tao ^c   Capen, Andrew R ^c   Huang, Jianping ^c   Joseph, Sajan ^c   Miller, Joel ^c   Benhadji, Karim A ^c   Brail, Les H ^c   Rosen, Lee S ^b  

^a South Texas Accelerated Research Therapeutics (START)   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c ELI LILLY AND COMPANY   (United States)

Author keywords

Cancer; LY2584702 tosylate; p70 S6 kinase (p70S6K); PI3 kinase

Indexed keywords

ANTINEOPLASTIC AGENT; LY 2584702; S6 KINASE; UNCLASSIFIED DRUG;

ADULT; ADVANCED CANCER; AGED; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER PATIENT; CLINICAL ARTICLE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EXPOSURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEMALE; GASTROINTESTINAL TOXICITY; HEARTBURN; HUMAN; HUMAN TISSUE; HYPOPHOSPHATEMIA; MALE; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NAUSEA; PANCREATITIS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; SKIN BIOPSY; SOLID TUMOR; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; VERY ELDERLY; VOMITING;

CANCER; LY2584702 TOSYLATE; P70 S6 KINASE (P70S6K); PI3 KINASE;

ADULT; AGED; AGED, 80 AND OVER; AREA UNDER CURVE; CHOLESTEROL; DRUG ADMINISTRATION SCHEDULE; FATIGUE; FEMALE; HUMANS; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; NAUSEA; NEOPLASMS; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PYRAZOLES; PYRIMIDINES; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SKIN; TIME FACTORS; TREATMENT OUTCOME; VOMITING;

EID: 84896740528     PISSN: 09598049     EISSN: 18790852     Source Type: Journal    
DOI: 10.1016/j.ejca.2013.11.039     Document Type: Article

References (18)

1. B.T. Hennessy, D.L. Smith, P.T. Ram, Y. Lu, and G.B. Mills Exploiting the PI3K/AKT pathway for cancer drug discovery Nat Rev Drug Discov 4 12 2005 988 1004
2. N. Rosen, and Q.B. She AKT and cancer-is it all mTOR? Cancer Cell 10 4 2006 254 256
3. R.J. Shaw, and L.C. Cantley Ras, PI(3)K and mTOR signalling controls tumour cell growth Nature 441 7092 2006 424 430
4. J. Huang, and B.D. Manning A complex interplay between Akt, TSC2 and the two mTOR complexes Biochem Soc Trans 37 Pt 1 2009 217 222
5. N.C. Barbet, U. Schneider, S.B. Helliwell, I. Stansfield, M.F. Tuite, and M.N. Hall TOR controls translation initiation and early G1 progression in yeast Mol Biol Cell 7 1 1996 25 42
6. G.J. Brunn, C.C. Hudson, A. Sekulic, J.M. Williams, H. Hosoi, and P.J. Houghton et al. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin Science 277 5322 1997 99 101
7. N.V. Dorrello, A. Peschiaroli, D. Guardavaccaro, N.H. Colburn, N.E. Sherman, and M. Pagano S6K1-and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth Science 314 5798 2006 467 471
8. A.C. Gingras, B. Raught, and N. Sonenberg EIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation Annu Rev Biochem 68 1999 913 963
9. S. Wullschleger, R. Loewith, and M.N. Hall TOR signaling in growth and metabolism Cell 124 3 2006 471 484
10. H.B. Jefferies, S. Fumagalli, P.B. Dennis, C. Reinhard, R.B. Pearson, and G. Thomas Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k EMBO J 16 12 1997 3693 3704
11. B. Raught, F. Peiretti, A.C. Gingras, M. Livingstone, D. Shahbazian, and G.L. Mayeur et al. Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases EMBO J 23 8 2004 1761 1769
12. S.G. Dann, A. Selvaraj, and G. Thomas MTOR Complex 1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer Trends Mol Med 13 6 2007 252 259
13. P. Therasse, S.G. Arbuck, E.A. Eisenhauer, J. Wanders, R.S. Kaplan, and L. Rubinstein et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst 92 3 2000 205 216
14. Torisel. Phildephia, PA: Wyeth Parmaceuticals Inc (A subsidiary of Phizer Inc); 2012.
15. Afinitor. East hanover, NJ: Novartis Pharmaceuticals Corp.; 2012.
16. K. Duvel, J.L. Yecies, S. Menon, P. Raman, A.I. Lipovsky, and A.L. Souza et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1 Mol Cell 39 2 2010 171 183
17. J. Tabernero, F. Rojo, E. Calvo, H. Burris, I. Judson, and K. Hazell et al. Dose-and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors J Clin Oncol 26 10 2008 1603 1610
18. Hoolebeque A, Houede N, Cohen E, Massard C, Italiano A, Westwood P, et al. A phase Ib trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in combination with erlotinib or everolimus in patients with solid tumour. Eur J Cancer 2014;50(5):876-84.