Phase i study of LY2603618, a CHK1 inhibitor, in combination with gemcitabine in Japanese patients with solid tumors

Anti-Cancer Drugs

Volumn 26, Issue 10, 2015, Pages 1043-1053

  Doi, Toshihiko ^a   Yoshino, Takayuki ^a   Shitara, Kohei ^a   Matsubara, Nobuaki ^b   Fuse, Nozomu ^a   Naito, Yoichi ^b   Uenaka, Kazunori ^c   Nakamura, Takashi ^c   Hynes, Scott M ^c   Lin, Aimee Bence ^c  

^a Department of Gastrointestinal Oncology ^*  (United States)

^b NATIONAL CANCER CENTER HOSPITAL EAST   (Japan)

^c ELI LILLY AND COMPANY   (United States)

Author keywords

checkpoint kinase 1; gemcitabine; Japanese; LY2603618; solid tumor

Indexed keywords

2',2' DEOXYDIFLUOROURIDINE; ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; CA 125 ANTIGEN; CA 19-9 ANTIGEN; DNA; DRUG METABOLITE; GAMMA GLUTAMYLTRANSFERASE; GEMCITABINE; HEMOGLOBIN; RABUSERTIB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; CHECKPOINT KINASE 1; DEOXYCYTIDINE; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PYRAZINE DERIVATIVE;

ADULT; ADVANCED CANCER; AGED; ALKALINE PHOSPHATASE BLOOD LEVEL; APPENDIX CANCER; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BLADDER CANCER; BLOOD TOXICITY; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER STAGING; CANCER SURVIVAL; CECUM CANCER; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; COHORT ANALYSIS; COLON CANCER; DECREASED APPETITE; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELIMINATION HALF-LIFE; EPIDERMOID TUMOR; ESOPHAGUS CANCER; FATIGUE; FEMALE; FEVER; HUMAN; JAPANESE (PEOPLE); LEUKOCYTE COUNT; LUNG CANCER; MALE; MAXIMUM PLASMA CONCENTRATION; MIDDLE AGED; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROENDOCRINE TUMOR; NEUTROPHIL COUNT; OPEN STUDY; OSTEOSARCOMA; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RECTUM CANCER; SIDE EFFECT; SOLID TUMOR; TONSIL CANCER; URETHRA CANCER; UROGENITAL TRACT TUMOR; VOMITING; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; METABOLISM; METASTASIS; NEOPLASMS; PATHOLOGY;

AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DEOXYCYTIDINE; FEMALE; HUMANS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASMS; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PYRAZINES;

EID: 84944068089     PISSN: 09594973     EISSN: 14735741     Source Type: Journal    
DOI: 10.1097/CAD.0000000000000278     Document Type: Article

References (40)

1. Jardim MJ, Wang Q, Furumai R, Wakeman T, Goodman BK, Wang XF. Reduced ATR or Chk1 expression leads to chromosome instability and chemosensitization of mismatch repair-deficient colorectal cancer cells. Mol Biol Cell 2009; 20:3801-3809.
2. Zhao B, Bower MJ, McDevitt PJ, Zhao H, Davis ST, Johanson KO, et al. Structural basis for Chk1 inhibition by UCN-01. J Biol Chem 2002; 277:46609-46615.
3. Nowsheen S, Yang ES. The intersection between DNA damage response and cell death pathways. Exp Oncol 2012; 34:243-254.
4. McNeely S, Beckmann R, Bence Lin AK. CHEK again: revisiting the development of CHK1 inhibitors for cancer therapy. Pharmacol Ther 2014; 142:1-10.
5. Tapia-Alveal C, Calonge TM, O'Connell MJ. Regulation of chk1. Cell Div 2009; 4:8.
6. Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 1997; 277:1497-1501.
7. Pabla N, Bhatt K, Dong Z. Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints. Proc Natl Acad Sci USA 2012; 109:197-202.
8. Zhang Y, Hunter T. Roles of Chk1 in cell biology and cancer therapy. Int J Cancer 2014; 134:1013-1023.
9. Helleday T. Amplifying tumour-specific replication lesions by DNA repair inhibitors-a new era in targeted cancer therapy. Eur J Cancer 2008; 44:921-927.
10. Nogueira A, Assis J, Catarino R, Medeiros R. DNA repair and cytotoxic drugs: the potential role of RAD51 in clinical outcome of non-small-cell lung cancer patients. Pharmacogenomics 2013; 14:689-700.
11. Zhao H, Watkins JL, Piwnica-Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiationinduced S and G2 checkpoints. Proc Natl Acad Sci USA 2002; 99:14795-14800.
12. Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev 2000; 14:1448-1459.
13. Zhu Y, Hu J, Hu Y, Liu W. Targeting DNA repair pathways: a novel approach to reduce cancer therapeutic resistance. Cancer Treat Rev 2009; 35:590-596.
14. Karnitz LM, Flatten KS,Wagner JM, Loegering D, Hackbarth JS, Arlander SJ, et al. Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. Mol Pharmacol 2005; 68:1636-1644.
15. Morgan MA, Parsels LA, Parsels JD, Mesiwala AK, Maybaum J, Lawrence TS. Role of checkpoint kinase 1 in preventing premature mitosis in response to gemcitabine. Cancer Res 2005; 65:6835-6842.
16. Dent P, Tang Y, Yacoub A, Dai Y, Fisher PB, Grant S. CHK1 inhibitors in combination chemotherapy: thinking beyond the cell cycle. Mol Interv 2011; 11:133-140.
17. King C, Diaz H, Barnard D, Barda D, Clawson D, Blosser W, et al. Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs 2014; 32:213-226.
18. Weiss GJ, Donehower RC, Iyengar T, Ramanathan RK, Lewandowski K, Westin E, et al. Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer. Invest New Drugs 2013; 31:136-144.
19. Calvo E, Richards D, Braiteh F, Von Hoff DD, McWilliams RR, Becerra C, et al. Dose determination of LY2603618, a Chk1 inhibitor, administered in combination with gemcitabine in patients with advanced cancer. Mol Cancer Ther 2011; 10 (Suppl):11.
20. Calvo E, Chen VJ, Marshall M, Ohnmacht U, Hynes SM, Kumm E, et al. Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer. Invest New Drugs 2014; 32:955-968.
21. CTCAE. 2006. Common terminology criteria for adverse events, version 3.0. Cancer Therapy Evaluation Program. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic-applications/docs/ctcaev3.pdf. [Accessed 15 June 2015].
22. MedDRA. 2013. The Medical Dictionary for Regulatory Activities (MedDRA). Available at: http://www.meddra.org. [Accessed 15 June 2015].
23. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228-247.
24. Gormally E, Caboux E, Vineis P, Hainaut P. Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. Mutat Res 2007; 635:105-117.
25. Schwarzenbach H. Circulating nucleic acids and protease activities in blood of tumor patients. Expert Opin Biol Ther 2012; 12 (Suppl 1):S163-S169.
26. Gonzalez R, Silva JM, Sanchez A, Dominguez G, Garcia JM, Chen XQ, et al. Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients: follow-up study and prognostic significance. Ann Oncol 2000; 11:1097-1104.
27. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11:426-437.
28. Linder S, Havelka AM, Ueno T, Shoshan MC. Determining tumor apoptosis and necrosis in patient serum using cytokeratin 18 as a biomarker. Cancer Lett 2004; 214:1-9.
29. Kramer G, Erdal H, Mertens HJ, Nap M, Mauermann J, Steiner G, et al. Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res 2004; 64:1751-1756.
30. Akaza H, Naito S, Usami M, Miki T, Miyanaga N, Taniai H. Japanese Gemcitabine Study Group. Efficacy and safety of gemcitabine monotherapy in patients with transitional cell carcinoma after cisplatin-containing therapy: a Japanese experience. Jpn J Clin Oncol 2007; 37:201-206.
31. Tanaka T, Ikeda M, Okusaka T, Ueno H, Morizane C, Hagihara A, et al. Prognostic factors in japanese patients with advanced pancreatic cancer treated with single-agent gemcitabine as first-line therapy. Jpn J Clin Oncol 2008; 38:755-761.
32. Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer 2010; 103:469-474.
33. Arlander SJ, Eapen AK, Vroman BT, McDonald RJ, Toft DO, Karnitz LM. Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress. J Biol Chem 2003; 278:52572-52577.
34. Hoffmann AC, Wild P, Leicht C, Bertz S, Danenberg KD, Danenberg PV, et al. MDR1 and ERCC1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia 2010; 12:628-636.
35. Ozcan MF, Dizdar O, Dincer N, Balc? S, Guler G, Gok B, et al. Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy. Urol Oncol 2013; 31:1709-1715.
36. Bowman KJ, Al-Moneef MM, Sherwood BT, Colquhoun AJ, Goddard JC, Griffiths TR, et al. Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo. Int J Cancer 2014; 134:1102-1111.
37. Eli Lilly and Company. GEMZAR (gemcitabine) US prescribing information for LY188011. Indianapolis, IN: Eli Lilly and Company; 2013.
38. Wickremsinhe ER, Hynes SM, Palmieri MD, Mitchell MI, Abraham TL, Rehmel JF, et al. Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous administration in patients with advanced and/or metastatic solid tumors. Xenobiotica 2014; 44:827-841.
39. Kamat AA, Bischoff FZ, Dang D, Baldwin MF, Han LY, Lin YG, et al. Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian carcinoma. Cancer Biol Ther 2006; 5:1369-1374.
40. Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, et al. Noninvasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497:108-112.