Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies.

Cancer Chemotherapy and Pharmacology
Prithviraj BoseSteven Grant

Abstract

Imatinib is an inhibitor of the Bcr-Abl tyrosine kinase; however, resistance is common. Flavopiridol, a cyclin-dependent kinase (CDK) inhibitor, down-regulates short-lived anti-apoptotic proteins via inhibition of transcription. In preclinical studies, flavopiridol synergizes with imatinib to induce apoptosis. We investigated this novel combination regimen in patients with Bcr-Abl(+) malignancies. In a phase I dose-escalation study, imatinib was administered orally daily, and flavopiridol by 1 h intravenous infusion weekly for 3 weeks every 4 weeks. Adults with chronic myelogenous leukemia or Philadelphia chromosome-positive acute leukemia were eligible. Patients were divided into two strata based on peripheral blood and bone marrow blast counts. The primary objective was to identify the recommended phase II doses for the combination. Correlative pharmacokinetic and pharmacodynamic studies were also performed. A total of 21 patients received study treatment. Four dose levels were evaluated before the study was closed following the approval of the second-generation Bcr-Abl tyrosine kinase inhibitors (TKIs). Five patients responded, including four sustained responses. Four patients had stable disease. All but one responder, and a...Continue Reading

References

Aug 6, 1997·Journal of the National Cancer Institute·R SimonM C Christian
Sep 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A M SenderowiczE A Sausville
Jan 19, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W M StadlerE E Vokes
Apr 3, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G K SchwartzD Kelsen
Jun 30, 2001·The Journal of Biological Chemistry·S H Chao, D H Price
Mar 1, 1996·Echocardiography·Barry P. Rosenzweig, Erminia Guarneri
Sep 28, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antoinette R TanAdrian M Senderowicz
Oct 3, 2002·The Journal of Pharmacy and Pharmacology·Sven DefermePatrick Augustijns
Mar 15, 2003·The New England Journal of Medicine·Stephen G O'BrienUNKNOWN IRIS Investigators
Jul 25, 2003·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·James W JacobbergerCharles L Goolsby
Aug 7, 2003·Current Opinion in Pharmacology·Yun Dai, Steven Grant
Nov 5, 2003·Progress in Cell Cycle Research·Peter M FischerLaurent Meijer
Jun 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Geoffrey I Shapiro
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Antoinette R TanSandra M Swain
Aug 13, 2004·The New England Journal of Medicine·Michael F Clarke
May 18, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Manish A ShahGary K Schwartz
Jul 15, 2005·The New England Journal of Medicine·Daniela S Krause, Richard A Van Etten
Aug 27, 2005·Clinical Pharmacokinetics·Bin PengHorst Schran
Dec 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Judith E KarpKenneth S Bauer
Jul 20, 2007·The New England Journal of Medicine·Charles A Schiffer
Apr 17, 2009·Current Oncology·M A Dickson, G K Schwartz
Dec 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas S LinJohn C Byrd
Mar 31, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Beata HolkovaSteven Grant

❮ Previous
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Citations

Feb 13, 2014·British Journal of Cancer·A H BeesleyU R Kees
Oct 29, 2014·Cancers·Jonas CicenasMindaugas Valius
Jan 15, 2016·Cell Cycle·Fatima Morales, Antonio Giordano
Jul 21, 2015·Assay and Drug Development Technologies·Olivia PerwitasariRalph A Tripp
Sep 11, 2012·Journal of Cellular Biochemistry·Yaozhong HuHe Huang
Dec 17, 2014·Critical Reviews in Oncology/hematology·Ke Yang, Li-wu Fu
Jan 9, 2016·Asian Pacific Journal of Cancer Prevention : APJCP·Muhammad Haseeb, Shahid Hussain
Oct 22, 2014·Oncotarget·Angelika BergerRichard Moriggl
Dec 20, 2019·Thyroid : Official Journal of the American Thyroid Association·Alice NervoEmanuela Arvat
Oct 20, 2019·Nature Communications·Ingeborg MenzlVeronika Sexl

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