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Vincristine

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by

Laura Duclos

on 7 March 2013

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Transcript of Vincristine

Margaret Craft and Laura Duclos Vincristine History Isolated from Vinca rosea in 1963 by Johnson et al. Acute leukemia
Hodgkin's and non-Hodgkin's lymphoma
Neuroblastoma
Rhabdomyosarcoma
Ewing's sarcoma
Wilm's tumor
Multiple myeloma
Chronic leukemias
Thyroid cancer Administered intravenously by slow IV push
(Fatal if given intrathecally).
Concentration based on weight. Dosage Two known mechanisms of resistance Resistance References methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2(7),3,5,13-tetraene-10-carboxylate IUPAC name: Microtubule Overview Vincristine Pathway Neuropathy
Cellulitis
Hair loss
Low blood count
Constipation Specific proteins become more pronounced in
Vincristine resistant cells.
-Multi-drug resistance associated protein
-Lung resistant protein Drug efflux pumps Changes in tubulin:
-Altered tubulin- decreased binding affinity of Vincristine
-Different tubulin isoforms
-Altered microtubule stability- due to shifting equilibrium between soluble and microtubule-bound tubulin Types of Cancer Side Effects Irving S. Johnson, James G. Armstrong, Marvin Gorman, J. Paul Bernett Jr. Nomenclature Leurocristine- until 1970s
Generic name: Vincristine
Commercially known today as:
-Oncovin (1963)
-Vincrex (1988, discontinued)
-Vincasar PFS (1999)
-Onco TCS (2004)
-Current trials- Marqibo (2012) Interactions Live or regular vaccines
Grapefruit juice
Boceprevir
Cobicistat Cocktails Gidding, C. E. M., Kellie, S. J., Kamps, W. A., & de Graaf, S. S. N. (1999). Vincristine revisited. Critical Reviews in Oncology/Hematology, 29(3), 267-287. Yoshidaa, K., Nagai, T., Ohminea, K., Uesawaa, M., & Sripayapa, P. (2011). Vincristine potentiates the anti-proliferative effect of an aurora kinase inhibitor, ve-465, in myeloid leukemia cells. Biochemical Pharmacology, 82(12), 1884-1890.

Singh Jaggi, A., & Singh, N. (2012). Toxicology, 291(1-3), 1-9. http://www.drugbank.ca/drugs/DB00541 Gidding, E. C. et al. Vincristine revisited (1999) Singh Jaggi, A., & Singh, N. Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy. (2012). Singh Jaggi, A., & Singh, N. Mechanisms in cancer- chemotherapeutic drugs-induced peripheral neuropathy. (2012). -Vincristine sulfate or Oncovin: PCV (procarbazine, lomustine/CeeNu, vincristine (Vincasar PFS) and MOPP (Mustargen, Oncovin, procarabzine, prednisone)
-Used in at least 20 other FDA approved cocktails:
-BEACOPP or ChlVPP/EVA for Hodkin’s lymphoma
-m-BACOD, MACOP-B, COP/CVP, COPP, CHOP, ProMACE-CytaBOM – Non-Hodgkin’s lymphoma
-POMP- acute adult leukemia http://www.tevagenerics.com/default.aspx?pageid=3364&sortby=ProductNameControlledDrug&ProductNameControlledDrug=VINCASAR+PFS%C2%AE+%28Vincristine+Sulfate+Injection%2c+USP%29&BrandName=Vincristine+Sulfate+Injection&audience=hcp http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/vincristine http://www.flexyx.com/V/Vincrex.html http://www.cancer.gov/clinicaltrials/results/summary/2012/oligodendroglioma1112 http://jco.ascopubs.org/content/31/6/657.short http://www.stjude.org/stjude/v/index.jsp?vgnextoid=a06c061585f70110VgnVCM1000001e0215acRCRD http://oncologystat.com/drugs_and_regimens/chemo_regimens/vincristine.html http://investor.enzon.com/releasedetail.cfm?ReleaseID=137185 http://www.matulane.com/pro-treatments.asp
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