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)

Investigational New Drugs
Jennifer J KnoxLesley Seymour

Abstract

Hepatocellular carcinoma (HCC) remains a lethal treatment-resistant cancer with a median survival of <6 months in patients not considered candidates for radical surgical treatments. SB-715992 is a novel cytotoxic agent implicated in the inhibition of mitotic kinesin spindle protein (KSP). Based on evidence from preclinical models and phase I trials, we conducted a phase II trial of SB-715992 in chemo-naïve patients with advanced HCC. A non-randomized, non-blinded multicentre two-stage phase II study was completed examining the efficacy, toxicity, and pharmacokinetics of SB-715992 at 18 mg/m2 IV q 3 weeks, in patients with measurable locally advanced, metastatic or recurrent HCC. The predictive value of KSP in archival tumour was assessed. Fifteen patients with metastatic HCC received a median of 3 cycles of SB-715992. The most common grade 3+ toxicities were granulocytopenia, leukocytopenia, diarrhea and liver transaminase rise. Overall confirmed response rate was 0%. Seven (46%) patients had a best response of stable disease at the 8-week evaluation (median duration 3.9 months) Median time to progression was 1.61 months (95%CI = 1.31-3.94 months) SB-715992 plasma concentrations were comparable to those observed in the phase I ...Continue Reading

References

Mar 11, 1999·The New England Journal of Medicine·H B El-Serag, A C Mason
Oct 13, 1999·Seminars in Liver Disease·H BismuthR Adam
Mar 1, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R T PoonJ Wong
Sep 19, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J M Llovet, J Bruix
Nov 17, 2001·Current Opinion in Pharmacology·K W WoodJ R Jackson
Jan 24, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Josep M Llovet, Jordi Bruix
May 9, 2003·Surgical Oncology Clinics of North America·Philip J Johnson
Dec 4, 2003·Expert Opinion on Pharmacotherapy·John F PerryGeoffrey W McCaughan
Jun 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paulo M HoffJames L Abbruzzese
Mar 12, 2005·CA: a Cancer Journal for Clinicians·D Max ParkinPaola Pisani

❮ Previous
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Citations

Feb 4, 2009·Cancer Metastasis Reviews·Nicholas Keen, Stephen Taylor
Feb 26, 2013·European Journal of Medicinal Chemistry·Hala Bakr El-Nassan
Oct 5, 2010·Nature Reviews. Drug Discovery·Charles Dumontet, Mary Ann Jordan
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James W PurcellSylvaine Cases
Feb 27, 2013·Cancer Science·Xinran LiuKun Huang
May 18, 2011·Pediatric Blood & Cancer·Richard B LockMalcolm A Smith
Nov 1, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Austin DuffyTim F Greten
Oct 18, 2011·Seminars in Cell & Developmental Biology·James A D GoodFrank Kozielski
Aug 23, 2011·Bioorganic & Medicinal Chemistry·Delany RodriguezCharles B Shuster
May 26, 2011·Chemistry & Biology·Sergey TcherniukAriane Abrieu
Aug 1, 2013·Journal of Medicinal Chemistry·Ambily Nath Indu Viswanath, Ae Nim Pae
Dec 10, 2015·PloS One·Akihiro OhashiMasanori Okaniwa
Aug 17, 2010·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Jesús García-Foncillas, Eduardo Díaz-Rubio
Jul 25, 2012·Nature Reviews. Cancer·Oliver Rath, Frank Kozielski
Dec 10, 2019·Expert Opinion on Investigational Drugs·Esperanza Macarena AlgarínEnrique M Ocio
Dec 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vasiliki Sarli, Athanassios Giannis
Feb 28, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sanne R Martens-de KempRuud H Brakenhoff
Oct 2, 2014·Cancer Research·Xinran LiuKun Huang
Dec 15, 2020·Biochemical Pharmacology·Isabel Garcia-Saez, Dimitrios A Skoufias
Mar 3, 2021·Cancer Letters·Gerhard JungwirthChristel Herold-Mende
Jul 25, 2009·Journal of Cell Science·Karen E Gascoigne, Stephen S Taylor

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