Study type: Open label, dose escalation
Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4877 in Japanese Patients with Solid Tumors
Article first published online: 7 APR 2011
DOI: 10.1111/j.1753-5174.2011.00034.x
© 2011, Archives of Drug Information
Additional Information
How to Cite
Esaki, T., Seto, T., Ariyama, H., Arita, S., Fujimoto, C., Tsukasa, K., Kometani, T., Nosaki, K., Hirai, F. and Yagawa, K. (2011), Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4877 in Japanese Patients with Solid Tumors. Archives of Drug Information, 4: 23–31. doi: 10.1111/j.1753-5174.2011.00034.x
Study phase: Phase I
Study registration number: ClinicalTrials.gov, NCT00613652
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
Publication History
- Issue published online: 1 JUN 2011
- Article first published online: 7 APR 2011
References
- 1, , , , , . Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 1995;83:1159–69.
- 2, , , , , , et al. Antitumor activity of a kinesin inhibitor. Cancer Res 2004;64:3276–80.
- 3, , , , , , et al. Differential gene expression analysis of kinesin spindle protein in human solid tumors. Proc Am Soc Clin Oncol 2003;22:abst 535.
- 4, , , , . Overexpression of Eg5 causes genomic instability and tumor formation in mice. Cancer Res 2007;67:10138–47.
- 5. Spindle assembly in animal cells. Annu Rev Biochem 2000;69:95–114.
- 6, , , , . Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by anti-microtubule agents in human lung cancers. Am J Pathol 2003;163:1109–16.
- 7
- 8
- 9, , , . Mechanisms of Taxol resistance related to microtubules. Oncogene 2003;22:7280–95.
- 10, , , , , . Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999;286:971–4.
- 11, . Progress on kinesin spindle protein inhibitors as anti-cancer agents. Anticancer Agents Med Chem 2008;8:698–704.
- 12, , , . Effects of Eg5 knockdown on human prostate cancer xenograft growth and chemosensitivity. Prostate 2008;68:1283–95.
- 13, , , . Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol 2000;150:975–88.
- 14, , , , , . Validating the mitotic kinesin Eg5 as a therapeutic target in pancreatic cancer cells and tumor xenografts using a specific inhibitor. Biochem Pharmacol 2008;76:169–78.
- 15, , , , , , et al. K858, a novel inhibitor of mitotic kinesin Eg5 and antitumor agent, induces cell death in cancer cells. Cancer Res 2009;69:3901–9.
- 16, , , , , , et al. Characterization of the kinesin spindle protein inhibitor AZD4877. AACR Annual Meeting 2010;abst 4429.
- 17, , , , , , et al. Clinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors. J Clin Oncol 2008;26(15S):abst 2501.
- 18World Medical Association (WMA). Declaration of Helsinki. Ethical principles for medical research involving human subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964. Available at: http://www.wma.net/en/30publications/10policies/b3/index.html (accessed October 2007).
- 19, . Clinical Pharmacokinetics: Concepts and Applications. 3rd edition. Philadelphia, PA.: Lippincott, Williams & Wilkins; 1995.
- 20, , , . Kinesin motor proteins as targets for cancer therapy. Cancer Metastasis Rev 2009;28:197–208.
- 21, , , , , , et al. A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168). Invest New Drugs 2008;26:265–72.
- 22, , , , , , et al. A phase II study of ispinesib (SB-715992) in patients with metastatic or recurrent malignant melanoma: a National Cancer Institute of Canada Clinical Trials Group trial. Invest New Drugs 2008;26:249–55.
- 23, , , , , , et al. Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck. Invest New Drugs 2008;26:257–64.
- 24, , , , , , et al. A University of Chicago consortium phase II trial of SB-715992 in advanced renal cell cancer. Clin Genitourin Cancer 2008;6:21–4.
- 25, , , , , , et al. Southwest Oncology Group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes. Clin Genitourin Cancer 2008;6:103–9.

