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New treatment options for lung cancer

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New treatment options for lung cancer Lung cancer is a leading cause of death world wide 90% of lung cancer is caused by smoking 20% of patients are suitable for ... – PowerPoint PPT presentation

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Title: New treatment options for lung cancer


1
New treatment options for lung cancer
2
  • Lung cancer is a leading cause of death world
    wide
  • 90 of lung cancer is caused by smoking
  • 20 of patients are suitable for surgery
  • 5 of all cases have 5 year survival

3
  • Most of the patients are in advanced stages and
    have very poor prognosis
  • Only 20 of patients are operable and only 5 of
    all cases survive 5 years
  • In general, patients with untreated lung cancer
    survive 8 months

4
  • Lung cancer is classified based on TNM system
    Tumor, Node, Metastasis)
  • The most common among lung cancers is non-small
    cell lung carcinoma (NSCLC)
  • Diagnosis by history and x-ray
  • Spiral CT screening
  • Surgery is a treatment of choice. (Chemotherapy,
    radiation)
  • Cure is rare

5
New treatment options
  • To survive and replicate cancer cells have very
    complex molecular pathways. Many epithelial
    tumors have abnormally activated epidermal growth
    factor (EGF). Several mechanisms lead to the
    activation of epidermal growth factor receptor
    (EGFR). This activation promotes series of
    reactions.
  • Two classes of EGFR anti-cancer agents
  • Erlotinib
  • Cetuximab


6
Erlotinib (Tarceva)
7
Erlotinib (Tarceva)
  • Erlotinib is an anti EGFR tyrosine kinase
    inhibitor. This drug has been approved for
    treatment of the patients with locally advanced
    or metastatic non small cell lung cancer after
    failure at least one prior chemotherapy regimen.
    It was approved in U.S. in November 2004.
  • Erlotinib is the only EGFR TKI therapy that have
    shown to improve the survival for NSCLC patients
    (6.7 months vs. 4.7 months for erlotinib and
    placebo respectively)
  • Erlotinib has proved to be safe for patients.
    Only 5 of patients had to discontinue treatment
    because of toxicity.

8
Erlotinib (Tarceva)
  • Some groups of patients may benefit more from
    this drug. They are female patients, nonsmokers,
    patients of Asian decent, and patients with
    adenocarcinoma.
  • The most recent research of 2006 made a discovery
    of EGFR mutations in tumor cells. This mutant
    EGFR is required for tumor maintenance.
    Surprisingly, Erlotinib was found to be more
    efficacious in mutant EGFR (Mendelsohn, 2006)

9
Iressa (Gefitinib)
  • Iressa (Gefitinib) is very similar to Erlotinib.
    It was the first selective EGFR inhibitori.
    Iressa reseived accelerated approval based on the
    data from phase II study. However, Iressa failed
    to improve a survival advantage in confirmatory
    trials requested by FDA.
  • Some scientists have speculated that Iressa and
    Tarceva had different interactions depending on
    the type of mutations in EGF receptors in human
    lung cancer. There are at least twenty different
    mutations in EGFR and scientists do not know if
    the same drug has the same effect for every
    mutation.
  • Another issue that has been discussed by research
    community was the use of different doses,
    suggesting that higher dose of Iressa was still
    probably effective (Twombly, 2006).

10
Cetuximab
  • The second class of EGFR agents is represented by
    Cetuximab.
  • It is a MONOCLONAL ANTIBODY that binds to EGFR
    and inhibits intracellular phosphorylation of
    EGFR and its signaling pathways.
  • Cetuximab is less potent than Erlotinib/Gefinib,
    it has its definite advantages. Cetuximab
    demonstrated to be effective on Gefitinib
    resistant mutant EGFR

11
Bevasizumab
12
Bevasizumab
  • Angiogenesis is one of the hallmarks of tumor
    formation. Majority of NSCLC tumors express
    vascular endothelial growth factor (VEGF).
    Studies proved that the higher expression of VEGF
    correlate with poor prognosis for lung cancer
    patients (Herbst, 2006).
  • Bevasizumab is a recombinant humanized monoclonal
    antibody against VEGF

13
  • Molecular pathways involved in stimulation and
    proliferation of cancer cells are involved in
    multiple levels. If one molecular target is
    blocked by anti-cancer agent, the others can be
    an escape routes for cancer cell stimulators.
  • This concept brought the next step in exploring
    possibilities of anti-cancer research. Combining
    drugs that affect different pathways can have
    additional clinical benefits (Sandler, 2006)

14
Combined therapy
  • Based on this concept, some investigators have
    speculated that the use of EGFR TKI with new
    agiogenesis inhibitors can be more efficacious.
    Preliminary data has shown no pharmacokinetic
    interaction between Erlotinib and Bevasizumab.
    The median overall survival for the treated
    patients was 12.6 months vs. 4 months for control
    group, with progression free survival of 6.2
    months vs. 2.5 months for untreated controls.

15
Statins
  • Lovastatin is inhibitor of 3-NMG CoA reductase.
    It leads to the inhibition of EGF-induced EGFR
    autophosphorylation and its signaling cascade
    within 24 hours.
  • Studies of combining Lovastatin and Erlotinib
    showed inhanced inhibition and cytotoxisity in a
    variety of cell lines. However, combinig
    Lovastatin and Erlotinib is contraindicated
    because of high risk of toxicity (both drugs are
    metabolized by CYP3A4).

16
Rosuvastatin Erlotinib
  • New possible alternative is mevolanate pathway
    inhibitor Rosuvastatin. The studies of combining
    Erlotinib and Rosuvastatin are proposed for a
    phase I/II in advanced non-small cell lung cancer.

17
COX-2 inhibitors
  • Lung tumors induce very immunosuppressive
    microenvironment. This may explain a very high
    unresponsiveness to immunological-based
    therapies. To enhance immunotherapy the use of
    COX-2 inhibitors was suggested. Although this
    mechanism is poorly understood, it has shown some
    effect on improvement in immunotherapy. Blocking
    arginase I through careful use of COX-2
    inhibitors promoted better outcomes of
    immunotherapy of lung cancer (Rodriguez, 2006).

18
Lung cancer blood test
  • A team of University of Kentucky Chandler Medical
    Center researchers has been working on developing
    the blood test to detect lung cancer in early
    stages.
  • The blood test identifies bodys own immune
    response to tumors.
  • This test is 90 accurate and diagnostic for
    lung cancer at early stages in the patients with
    high risk factors such as smoking, family history
    and age. This test can correctly predict NSCLC
    years before CT scan can detect it.

19
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