A phase II randomized study of cisplatin-pemetrexed plus either enzastaurin or placebo in chemonaive patients with advanced non-small cell lung cancer

Oncology

Volumn 82, Issue 1, 2012, Pages 25-29

  Vansteenkiste, Johan ^a   Ramlau, Rodryg ^b   Von Pawel, Joachim ^d   San Antonio, Belen ^g   Eschbach, Corinna ^e   Szczesna, Aleksandra ^c   Kennedy, Liam ^h   Visseren Grul, Carla ^h   Chouaki, Nadia ^h   Reck, Martin ^f  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

^c Regional Lung Diseases Hospital   (Poland)

^d Asklepios Hospital Munich Gauting   (Germany)

^e Asklepios Hospital Hamburg   (Germany)

^f KRANKENHAUS GROSSHANSDORF   (Germany)

^g ELI LILLY AND COMPANY   (Spain)

^h ELI LILLY AND COMPANY   (United States)

Author keywords

Cisplatin pemetrexed; Enzastaurin; Non small cell lung cancer

Indexed keywords

CISPLATIN; CYANOCOBALAMIN; DEXAMETHASONE; ENZASTAURIN; FOLIC ACID; PEMETREXED; PLACEBO;

ADULT; ADVANCED CANCER; ANEMIA; ARTHRALGIA; ARTICLE; CANCER CHEMOTHERAPY; CANCER PATIENT; CANDIDIASIS; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DUODENUM ULCER; DYSPNEA; FATIGUE; FEMALE; HUMAN; HYPERTENSION; HYPONATREMIA; LOADING DRUG DOSE; LUNG EMBOLISM; LUNG INFECTION; LUNG NON SMALL CELL CANCER; MALE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MYALGIA; NEUTROPENIA; OXYGEN SATURATION; PERICARDIAL EFFUSION; PHASE 2 CLINICAL TRIAL; PLEURA EFFUSION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT INFECTION; SIDE EFFECT; TACHYCARDIA; THORAX PAIN; THROMBOCYTOPENIA; VITAMIN SUPPLEMENTATION;

AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; CISPLATIN; DOUBLE-BLIND METHOD; FEMALE; GLUTAMATES; GUANINE; HUMANS; INDOLES; LUNG NEOPLASMS; MALE; MIDDLE AGED; PLACEBOS;

EID: 84856040615     PISSN: 00302414     EISSN: 14230232     Source Type: Journal    
DOI: 10.1159/000335268     Document Type: Article

References (14)

1. Felip E, Gridelli C, Baas P, Rosell R, Stahel R, Panel Members: Metastatic non-small cell lung cancer: Consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010. Ann Oncol 2011; 22: 1973-1980.
2. National Comprehensive Cancer Network 2007: NCCN clinical practice guidelines in oncology: Non-small cell lung cancer. http://www.nccn.org/ professionals/physician-gls/f-guidelines.asp (accessed May 25, 2010
3. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH, Eastern Cooperative Oncology Group: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92-98. (Pubitemid 34438899)
4. Nakajima E, Helfrich B, Chan D, Zhang Z, Hirsch FR, Chen V, Ma D, Bunn PA: Enzastaurin, a protein kinase C-beta-selective inhibitor, inhibits the growth of SCLC and NSCLC cell lines (abstract 13138). J Clin Oncol 2006; 24: 612s.
5. McNulty AM, Konicek BW, Lynch RL, Thornton D, Douglass L, Colligan B, Carter JH, Graff JAR: Enzastaurin (LY317615.HCl) suppresses signaling through the PKC and AKT pathways, inducing apoptosis, suppressing tumor-induced angiogenesis and reducing growth of human cancer xenografts (abstract 1332). Proc Am Assoc Cancer Res 2006; 47: 73.
6. Carducci MA, Musib L, Kies MS, Pili R, Truong M, Brahmer JR, Cole P, Sullivan R, Riddle J, Schmidt J, Enas N, Sinha V, Thornton DE, Herbst RS: Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer. J Clin Oncol 2006; 24: 4092-4099. (Pubitemid 46622284)
7. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapynaive patients with advanced-stage nonsmall-cell lung cancer. J Clin Oncol 2008; 26: 3543-3551.
8. Hanauske AR, Lahn M, Musib LC, Weigang-Köhler K, Yilmaz E, Graefe T, Kuenen B, Thornton D, McNealy P, Giaccone G: Phase Ib safety and pharmacokinetic evaluation of daily and twice daily oral enzastaurin in combination with pemetrexed in advanced/metastatic cancer. Ann Oncol 2009; 20: 1565-1575.
9. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: 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 2000; 92: 205-216.
10. Rademaker-Lakhai JM, Beerepoot LV, Mehra N, Radema SA, van Maanen R, Vermaat JS, Witteveen EO, Visseren-Grul CM, Musib L, Enas N, van Hal G, Beijnen JH, Schellens JH, Voest EE: Phase I pharmacokinetic and pharmacodynamic study of the oral protein kinase C beta-inhibitor enzastaurin in combination with gemcitabine and cisplatin in patients with advanced cancer. Clin Cancer Res 2007; 13: 4474-4481. (Pubitemid 47219716)
11. Camidge DR, Gail Eckhardt S, Gore L, O'Bryant CL, Leong S, Basche M, Holden SN, Musib L, Baldwin J, Darstein C, Thornton D, Finn RS, Britten CD: A phase I safety, tolerability, and pharmacokinetic study of enzastaurin combined with capecitabine in patients with advanced solid tumors. Anticancer Drugs 2008; 19: 77-84. (Pubitemid 350190970)
12. Oberschmidt O, Eismann U, Schulz L, Struck S, Blatter J, Lahn MM, Ma D, Hanauske AR: Enzastaurin and pemetrexed exert synergistic antitumor activity in thyroid cancer cell lines in vitro. Int J Clin Pharmacol Ther 2005; 43: 603-604. (Pubitemid 43009367)
13. Chiappori A, Bepler G, Barlesi F, Soria JC, Reck M, Bearz A, Barata F, Scagliotti G, Park K, Wagle A, Liepa AM, Zhao YD, Chouaki N, Iscoe N, von Pawel J: Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 2010; 5: 369-375.
14. Socinski MA, Raju RN, Stinchcombe T, et al: Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV nonsmall cell lung cancer. J Thorac Oncol 2010; 5: 1963-1969.