Gemcitabine plus enzastaurin or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer: Results of a Phase II, randomized, noncomparative study

Investigational New Drugs

Volumn 29, Issue 1, 2011, Pages 144-153

  Richards, Donald A ^a,b   Kuefler, Paul R ^a,c   Becerra, Carlos ^a,d   Wilfong, Lalan S ^a,b   Gersh, Robert H ^a,e   Boehm, Kristi A ^a   Zhan, Feng ^a   Asmar, Lina ^a   Myrand, Scott P ^f   Hozak, Rebecca R ^f   Zhao, Luping ^f   Gill, John F ^f   Mullaney, Brian P ^f   Obasaju, Coleman K ^f   Nicol, Steven J ^f  

^a US Oncology   (United States)

^b TEXAS ONCOLOGY   (United States)

^c Northern Arizona Hematology Oncology   (United States)

^d BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

^e Cancer Care Northwest   (United States)

^f ELI LILLY AND COMPANY   (United States)

Author keywords

Chemotherapy; Enzastaurin; Gemcitabine; Pancreatic cancer; Phase II

Indexed keywords

CA 19-9 ANTIGEN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; ENZASTAURIN; GEMCITABINE; GLYCOGEN SYNTHASE KINASE 3BETA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN KINASE C BETA; S6 KINASE;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANOREXIA; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER CONTROL; CANCER GROWTH; CANCER SURVIVAL; CONSTIPATION; DEHYDRATION; DIARRHEA; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG RESPONSE; DYSPNEA; FATIGUE; FEMALE; HUMAN; IMMUNOHISTOCHEMISTRY; LEUKOPENIA; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MUSCLE WEAKNESS; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PANCREAS CANCER; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA; VOMITING;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DEOXYCYTIDINE; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; INDOLES; MALE; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASM STAGING; PANCREATIC NEOPLASMS; QUALITY OF LIFE; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 79151469315     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-009-9307-8     Document Type: Article

References (25)

1. American Cancer Society: Detailed Guide: Pancreatic Cancer. What Are the Key Statistics About Cancer of the Pancreas? URL: http://www.cancer.org/docroot/ CRI/content/CRI-2-4-1X-What-are-the-key-statistics-for-pancreatic-cancer-34.asp? sitearea (accessed April 14, 2009)
2. JD Berlin P Catalano JP Thomas, et al. 2002 Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297 J Clin Oncol 20 3270 3275 1:CAS:528:DC%2BD38XmsF2rs74%3D 10.1200/JCO.2002.11.149 12149301
3. GP Stathopoulos K Syrigos G Aravantinos, et al. 2006 A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer Br J Cancer 95 587 592 1:CAS:528:DC%2BD28XovVWitLc%3D 10.1038/sj.bjc.6603301 16909140
4. JR Graff AM McNulty KR Hanna, et al. 2005 The protein kinase Cβ-selective inhibitor, enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts Cancer Res 65 7462 7469 1:CAS:528: DC%2BD2MXns1Wqsrc%3D 10.1158/0008-5472.CAN-05-0071 16103100
5. AR Hanauske O Oberschmidt H Hanauske-Abel, et al. 2007 Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cells and freshly explanted tumors investigated in in-vitro soft-agar cloning experiments Invest New Drugs 25 205 210 1:CAS:528:DC%2BD2sXltlartr8%3D 10.1007/s10637-007-9038-7 17347872
6. AC Spalding R Watson ME Davis, et al. 2007 Inhibition of protein kinase Cβ by enzastaurin enhances radiation cytotoxicity in pancreatic cancer cells Clin Cancer Res 13 6827 6833 1:CAS:528:DC%2BD2sXhtlSmu7fF 10.1158/1078-0432.CCR-07-0454 18006785
7. Llombart-Cussac A, Matias-Guiu X, Medina DM et al (2009) Enzastaurin inhibits in vivo GSK3β phosphorylation in early breast cancer. American Association of Cancer Research Annual Meeting, Abstract LB-256
8. Robertson M, Kahl B, Vose J et al (2005) A Phase II study of enzastaurin, a protein kinase C-β (PKCβ) inhibitor, in the treatment of relapsed diffuse large B-cell lymphoma (DLBCL). Blood (ASH Annual Meeting Abstracts) 106: Abstract 934
9. HA Fine L Kim C Royce, et al. 2005 Results from phase II trial of enzastaurin (LY317615) in patients with recurrent high grade gliomas J Clin Oncol 23 16s (suppl; abstr 1504)
10. Y Oh RS Herbst H Burris, et al. 2008 Enzastaurin, an oral serine/threonine kinase inhibitor, as second- or third-line therapy of non-small-cell lung cancer J Clin Oncol 26 1135 1141 1:CAS:528: DC%2BD1cXktVKit7o%3D 10.1200/JCO.2007.14.3685 18309949
11. P Therasse SG Arbuck EA Eisenhauer, et al. 2000 New guidelines to evaluate the response to treatment in solid tumors J Natl Cancer Inst 92 205 216 1:STN:280:DC%2BD3c7it1Gitg%3D%3D 10.1093/jnci/92.3.205 10655437
12. Eli Lilly and Company-Gemzar® (Gemcitabine HCl for Injection). URL: http://pi.lilly.com/us/gemzar.pdf (accessed 14 April 2009)
13. National Cancer Institute. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Publish date 9 August 2006. Available at: http://ctep.cancer.gov/ reporting/ctc.html (accessed 20 May 2009)
14. EL Kaplan P Meier 1958 Nonparametric estimation of incomplete observations J Am Stat Assoc 53 457 481 10.2307/2281868
15. R Miller D Siegmund 1982 Maximally selected chi-square statistics Biometrics 38 1011 1016 10.2307/2529881
16. C Spearman 1904 The proof and measurement of association between two things Amer J Psychol 15 72-101 1904
17. AH Ko J Hwang AP Venook, et al. 2005 Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer Br J Cancer 93 195 199 1:CAS:528:DC%2BD2MXmt1yhurs%3D 10.1038/sj.bjc.6602687 15999098
18. M Reni S Cereda G Balzano, et al. 2009 Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma Cancer 115 2630 2639 1:CAS:528:DC%2BD1MXotFOgsr0%3D 10.1002/cncr.24302 19353729
19. D Wong AH Ko J Hwang, et al. 2008 Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy Pancreas 37 269 274 10.1097/MPA.0b013e31816d8185 18815548
20. T Cartwright DA Richards KA Boehm 2008 Cancer of the pancreas: are we making any progress? A review of studies in the US Oncology Research Network Cancer Control 15 308 313 18813198
21. V Heinemann D Quietzsch F Gieseler, et al. 2006 Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer J Clin Oncol 24 3946 3952 1:CAS:528:DC%2BD28Xps1Sit78%3D 10.1200/JCO.2005.05.1490 16921047
22. R Herrmann G Bodoky T Ruhstaller, et al. 2007 Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group J Clin Oncol 25 2212 2217 1:CAS:528:DC%2BD2sXnsVShtbw%3D 10.1200/JCO.2006.09.0886 17538165
23. H Oettle D Richards RK Ramanathan, et al. 2005 A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer Ann Oncol 16 1639 1645 1:STN:280: DC%2BD2MvpvFKhsg%3D%3D 10.1093/annonc/mdi309 16087696
24. DA Richards H Oettle WL Vervenne, et al. 2005 Randomized double-blind phase II trial comparing gemcitabine (GEM) plus LY293111 vs. GEM plus placebo in advanced adenocarcinoma of the pancreas J Clin Oncol 23 16s (suppl; abstr 4092)
25. AV Ougolkov ME Fernandez-Zapico DN Savoy, et al. 2005 Glycogen synthase kinase-3β participates in nuclear factor κB-mediated gene transcription and cell survival in pancreatic cancer cells Cancer Res 65 2076 2081 1:CAS:528:DC%2BD2MXisFGgtbg%3D 10.1158/0008-5472.CAN-04-3642 15781615