A phase I study of ispinesib, a kinesin spindle protein inhibitor, administered weekly for three consecutive weeks of a 28-day cycle in patients with solid tumors

Investigational New Drugs

Volumn 29, Issue 3, 2011, Pages 467-472

  Burris III, Howard A ^a   Jones, Suzanne F ^a   Williams, Daphne D ^c   Kathman, Steven J ^c   Hodge, Jeffrey P ^c   Pandite, Lini ^c   Ho, Peter T C ^c   Boerner, Scott A ^b   LoRusso, Patricia ^b  

^a SARAH CANNON RESEARCH INSTITUTE   (United States)

^b KARMANOS CANCER INSTITUTE   (United States)

^c GLAXOSMITHKLINE   (United States)

Author keywords

Ispinesib; Kinesin spindle protein; Mitosis; Pharmacokinetics; Phase I; Safety; SB 715992

Indexed keywords

ISPINESIB;

ADULT; ADVANCED CANCER; ALOPECIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER GRADING; CLINICAL ARTICLE; DIARRHEA; DOSE RESPONSE; DRUG CLEARANCE; DRUG CYTOTOXICITY; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HUMAN; INJECTION SITE PAIN; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; MALE; MAXIMUM PLASMA CONCENTRATION; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROPATHY; NEUTROPENIA; PANCREAS CANCER; PAPILLARY CARCINOMA; PHASE 1 CLINICAL TRIAL; PHLEBITIS; PRIORITY JOURNAL; PROSTATE CANCER; PUNCH BIOPSY; RECOMMENDED DRUG DOSE; SOLID TUMOR; THROMBOCYTOPENIA; TUMOR BIOPSY;

ADULT; ANTINEOPLASTIC AGENTS; BENZAMIDES; DEMOGRAPHY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; KINESIN; MALE; MITOTIC SPINDLE APPARATUS; NEOPLASMS; QUINAZOLINES;

EID: 79955627902     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-009-9374-x     Document Type: Article

References (22)

1. Wood KW, Cornwell WD, Jackson JR (2001) Past and future of the mitotic spindle as an oncology target. Curr Opin Pharmacol 1:370-377 (Pubitemid 33585986)
2. Miglarese MR, Carlson RO (2006) Development of new cancer therapeutic agents targeting mitosis. Expert Opin Investig Drugs 15:1411-1425 (Pubitemid 44615289)
3. Bergnes G, Brejc K, Belmont L (2005) Mitotic kinesins: prospects for antimitotic drug discovery. Current topics in medicinal chemistry 5:127-145 (Pubitemid 40514510)
4. Kapitein LC, Peterman EJ, Kwok BH, Kim JH, Kapoor TM, Schmidt CF (2005) The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks. Nature 435:114-118 (Pubitemid 40655918)
5. Blangy A, Lane HA, d'Herin P, Harper M, Kress M, Nigg EA (1995) Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83:1159-1169
6. Kashina AS, Baskin RJ, Cole DG, Wedaman KP, Saxton WM, Scholey JM (1996) A bipolar kinesin. Nature 379:270-272 (Pubitemid 26025214)
7. Tao W, South VJ, Diehl RE et al (2007) An inhibitor of the kinesin spindle protein activates the intrinsic apoptotic pathway independently of p53 and de novo protein synthesis. Mol Cell Biol 27:689-698 (Pubitemid 46080134)
8. Tao W, South VJ, Zhang Y et al (2005) Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly checkpoint and mitotic slippage. Cancer Cell 8:49-59 (Pubitemid 40991814)
9. Hedge P, Cogswell J, Carrick K et al (2003) Differential gene expression analysis of kinesin spindle protein in human solid tumors. Proc Am Assoc Cancer Res 22:535
10. Sakowicz R, Finer JT, Beraud C et al (2004) Antitumor activity of a kinesin inhibitor. Cancer Res 64:3276-3280 (Pubitemid 38581433)
11. Muller C, Gross D, Sarli V et al (2007) Inhibitors of kinesin Eg5: antiproliferative activity of monastrol analogues against human glioblastoma cells. Cancer Chemother Pharmacol 59:157-164 (Pubitemid 44885145)
12. Marcus AI, Peters U, Thomas SL et al (2005) Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells. J Biol Chem 280:11569-11577 (Pubitemid 40418469)
13. Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ (2000) Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol 150:975-988
14. Lad L, Luo L, Carson JD et al (2008) Mechanism of inhibition of human KSP by ispinesib. Biochemistry 47:3576-3585 (Pubitemid 351399246)
15. Johnson RK, McCabe FL, Cauder E et al (2002) SB-715992, a potent and selective inhibitor of the mitotic kinesin KSP, demonstrates broad-spectrum activity in advanced murine tumors and human tumor xenografts. Proc Am Assoc Cancer Res 43:A1335
16. Rodon J, Till E, Patnaik A et al (2006) Phase I study of ispinesib (SB-715992), a kinesin spindle protein inhibitor, in combination with capecitabine in patients with advanced solid tumors. Eur J Canc Suppl 4:193, Abstr 640
17. Shahin MS, Braly P, Rose P et al (2007) A phase II, open-label study of ispinesib (SB-715992) in patients with platinum/taxane refractory or resistant relapsed ovarian cancer. J Clin Oncol 25:5562
18. Heath EI, Alousi A, Eder JP et al (2006) A phase I dose escalation trial of ispinesib (SB-715992) administered days 1-3 of a 21-day cycle in patients with advanced solid tumors. J Clin Oncol 24:2026
19. Chu QS, Holen KD, Rowinsky EK et al (2004) Phase I trial of novel kinesin spindle protein (KSP) inhibitor SB-715992 IV Q 21 days. J Clin Oncol 22:2078
20. Blagden SP, Molife LR, Seebaran A et al (2008) A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours. Br J Cancer 98:894-899 (Pubitemid 351341614)
21. Lee CW, Belanger K, Rao SC et al (2008) 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 26:249-255 (Pubitemid 351579684)
22. Tang PA, Siu LL, Chen EX et al (2008) Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck. Invest New Drugs 26:257-264