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Chemotherapy of Medulloblastoma

VIEWS: 5 PAGES: 14

									Chemotherapy of
Medulloblastoma
    By: Minh Trinh
             Objectives
Briefly describe chemotherapy of
medulloblastoma
Discuss different regimens used for
therapy and their mechanisms,
administrations, how they are supplied,
dosages for certain drugs, and side effects
Relate therapy to Jorge P.
Conclusion
  Overview of chemotherapy of
       medulloblastoma
At this time, the role of chemotherapy in
medulloblastoma is primarily an additional
treatment following surgery and radiation
For average-risk disease, children from 3-
10 who received chemotherapy and
radiation had a superior survival rate
3 year progression free survival rate 80%
Regiments used in chemotherapy
Methotrexate – tablets, powder/solution for injection;
folate antimetabolite
Lomustine (CCNU) - capsule; an oral nitrosurea alkylating
agent
Etoposide – solution for injection; cell cycle-phase specific
antineoplastic agent
Vincristine – solution for injection; plant-derived vinca
alkaloid which is extracted from Catharanthus rosea
Cyclophosphamide – tablets or powder for injection;
bifunctional alkylating agent related to nitrogen mustard
Cisplatin – solution for injection; planar platinum
bifunctional alkylating agent
Carboplatin – powder/solution for injection; platinum
compound related to cisplatin, less cytotoxic
              Details of methotrexate
    Mechanism of action
-   Competitively inhibits dihydrofolate
    reductase
-   Interferes with DNA/RNA synthesis
-   Cell cycle-specific (S-phase or G1 into
    S-phase)
    Administration
-   Intravenously, orally, intraventricularly
    (Jorge P.), intrathecally,
    intramuscularly
    Dosing
-   Intraventricular dosing guidelines do
    not exist, however in children 2mg/day
    is commonly used (Jorge P.)
    Side Effects
-   Severe: changes in vision, diarrhea,
    confusion                                   http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/PC_IM
-   Mild: Hair loss, nausea, eye irritation     AGE/APRD00353_ZOOM.gif
       Details of lomustine (CCNU)
    Mechanism of action
-   Inhibits DNA replication, RNA
    transcription, and nucleic acid
    function
-   The chloroethyl group alkylates
    nucleic acids and cell proteins to
    form DNA-DNA or DNA-protein
    crosslinks
•   Administration
-   Orally
•   Side effects
-   Severe: difficulty breathing, low
    blood count, signs of infection
-   Mild: confusion, hair loss, loss of
    appetite
                                          http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/PC_IMA
                                          GE/APRD00292_ZOOM.gif
                 Details of etoposide
     Mechanism of action
-   Active during G2
-   Binds to a complex of DNA and
    topoisomerase II
-   Apoptosis
    Administration
-   Orally or intravenously
    Side Effects
-   Severe: tarry stools, blood in urine,
    difficulty breathing
-   Mild: diarrhea, hair loss, headache
                                            http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/PC_IMA
                                            GE/APRD00239_ZOOM.gif
                   Details of vincristine
    Mechanism of action
-   Binds to the alpha, beta sites of tubulin
-   Interferes with microtubules which
    compose mitotic spindle fibers
-   Cell cycle arrest in metaphase
•   Administration
-   Intravenously
•   Dosing
-   1.5 mg/m^2 BSA
-   For Jorge P, his BSA is 0.61 m^2 so
    he would get (0.61 m^2 * 1.5mg/m^2 =
    0.915 mg/day
•   Side effects
-   Severe: constipation, fever, rash
-   Mild: hair loss, loss of appetite, feeling
    tired                                        http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/PC_IMAG
                                                 E/APRD00495_ZOOM.gif
        Details of cyclophosphamide
    Mechanism of action
-   Prodrug that requires hepatic activation in order to be
    cytotoxic
-   Activated in liver by cytochrone P450 enzymes
-   Phosphoramide mustard is the active moiety
-   Forms intrastrand and interstrand DNA-DNA
    crosslinks.
    Administration
-   Orally or intravenously
    Dosing
-   800 mg/m^2 BSA
-   For Jorge P. (0.61 m^2 * 800 mg/m^2 = 488
    mg/dose)
    Side effects
-   Severe: blood in urine, signs of infection, confusion
-   Mild: decreased appetite, hair loss, muscle pains
                                                              http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/PC_I
                                                              MAGE/APRD00408_ZOOM.gif
                  Details of cisplatin
    Mechanism of action
-   Intracellularly, loses its chloride
    groups making it electrophilic.
-   Forms interstrand/intrastrand DNA &
    RNA crosslinks
    Administration
-   Intravenously or intraarterially
    Side effects
-   Severe: difficulty breathing, hearing
    loss, nausea and vomiting
-   Mild: blurred vision, changes in
    taste, loss of appetite
                                            http://redpoll.pharmacy.ualberta.ca/drugbank/drugBa
                                            nk/PC_IMAGE/APRD00359_ZOOM.gif
                 Details of carboplatin
    Mechanism of action
-   Hydroxylated by water to form the
    active compound, slower than
    cisplatin.
-   Works like other bifunctional alkylating
    agents
    Administration
-   Intravenously
    Side effects
-   Severe: changes in eyesight, hearing
    loss, difficulty breathing
-   Mild: fatigue, loss of appetite, loss of
    hair, metallic taste


                                               http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/PC_IMAGE/AP
                                               RD00466_ZOOM.gif
              Jorge P.
  Methotrexate
- 2mg/day
  Cyclophosphamide
- 488 mg/dose
  Vincristine
- 0.915 mg/dose
            Conclusion
Chemotherapy usually used after radiation
or surgical therapy
Wide variety of different regimens used
each with different dosages,
administrations, and side effects
Jorge P was administered methotrexate,
vincristine, and cyclophosphamide
                  References
Oncolink. 1994. Abraham Cancer Center of the University of
Pennsylvania. 1 March 2007
http://www.oncolink.org/types/article.cfm?c=14&s=78&ss=783&id=9
484
Mcdonald T., MD. Emedicine. 21 July 2006. Web MD. 1 March
2007. http://www.emedicine.com/ped/topic1396.htm
Clinical Pharmacology. CD-ROM. Tampa: Gold Standard, 1994-
2005
DrugBank. February 1, 2006. Genome Alberta & Genome Canada
and Departments of Computing Science & Biological Sciences at
the University of Alberta. 1 March 2006.
http://redpoll.pharmacy.ualberta.ca/drugbank/

								
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