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New treatment options for lung cancer


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

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

  • 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

  • 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,
  • Cure is rare

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
  • Two classes of EGFR anti-cancer agents
  • Erlotinib
  • Cetuximab

Erlotinib (Tarceva)
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.

Erlotinib (Tarceva)
  • Some groups of patients may benefit more from
    this drug. They are female patients, nonsmokers,
    patients of Asian decent, and patients with
  • 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)

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
  • 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).

  • The second class of EGFR agents is represented by
  • 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

  • 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

  • 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)

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.

  • 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).

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.

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).

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
  • 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.

  • References
  • Auberger J, Loeffler-Ragg J, Wurzer W, Hibe W.
    Targeted therapies in non-small cell lung cancer
    proven concepts and unfulled promises. Curr
    Cancer Drug Targtes. 2006 Jun 6(4)271-94.
  • Bandyopadhyay A, Agyin JK, Wang L, Tang Y, Lei X,
    Story BM, et al. Inhibition of pulmonary and
    skeletal metatstasis by a transforming growth
    factor-beta type I receptor kinase inhibitor.
    Cancer Res. 2006 Jul 166(13)6714-21.
  • Belvedere O, Grossi F. Lung cancer highlits from
    Asco 2005. Oncologist. 2006 Jan11(1)39-50.
  • Bezjak A, Tu D, Seymour L, Clark G, Trajkovic
    A,Zukin M, et al. Symptom improvement in lung
    cancer patients treated with erlotinib quality
    of life analysisnof the National Cancer Institute
    of Canada Clinical Trials Group Study BR.21. J
    Clin Oncol. 2006 Aug 2024(24)3831-7.
  • Blackhall F, Ranson M, Thatcher N. Where next for
    gefitinib in patients with lung cancer? Lancet
    Oncol. 2006 Jun7(6)499-507.
  • Comis RS. The current situation Erlotinib
    (Tarceva) and Gefitinib (Iressa) in non-small
    cell lung cancer. Oncologist. 2006
  • Dalwadi H, Krysan K, Heuze-Vourch N, Dohadwala M,
    Elashaff D, Sharma S, Casalano N, Lichenstein A,
    Dubinett S. Cyclogenase-2-dependent activation of
    signal transducer and activator of transcription
    3 by interleukin-6 in non-small cell lung cancer.
    Clin. Cancer. Res. 2005 Nov 1 11 (21) 7674-82.
  • Dimitroulakos J, Lorimer IA, Goss G. Strategies
    to enhance epidermal growth factor inhibition
    targeting the mevalonate pathway. Clin. Cancer.
    Res. 2006 Jul 1512(14 Pt 2)4426s-4413s.
  • Dy GK, Adjei AA. Angiogenesis inhibitors in lung
    cancer a promice fulfilled. Clin Lung
    Cancer.2006 May7 Suppl 4S 145-9.
  • Fang LC, Komaki R, Allen P, Guerrero T, Mohan R,
    Cox JD. Comparison of outcomes for patients with
    medically inoperable Stage I non-small-cell lung
    cancer treated with two dimensional vs. three
    dimensional radiotherapy. Int J Radiat Oncol Biol
    Phys. 2006 Sep 166(1)108-16.
  • Heymach JV, Nilsson M, Blumenschein G,
    Papadimitrakopoulou V, Herbst R. Epidermal growth
    factor receptor inhibitors in development for the
    treatment of non-small cell lung cancer. Clin
    Cancer Res. 2006 Jul 1512(14 Pt 2)4441s-4445s.
  • Ji H, Zhao X, Yuza Y, Shimamura T, Li D,
    Protopopov A, et al. Epidermal growth factor
    receptor variant III mutations in lung
    tumorigenesis and sensitivity to tyrosine kinase
    inhibitors. Proc Natl Acad Sci USA. 2006 May
  • Johnson BE, Janne PA. Rationale for a phase II
    trial of Pertuzamub, a HER-2 dimerization
    inhibitor, in patients with non-small cell lung
    cancer. Clin Cancer Res. 2006 Jul 1512(14 Pt
  • Kris MG. How tadays developments in the
    treatment of non-smalllung cancer will change
    tomorrows standards of care. Oncologist. 2005
    Oct10 Suppl 223-9.
  • Maione P, Gridelli C, Troiani T, Ciardiello F.
    Combining targeted therapies and drugs with
    multiple targets in the treatment of NSCLC.
    Oncologist. 2006 Mar11(3)274-84.
  • Mendelsohn J, Baselga J. Epidermal growth factor
    receptor targeting in cancer. Semin Oncol. 2006
  • Politi K, Zakowski MF, Fan PD, Schonfeld EA, Pao
    W, Varmus HF. Lung adenocarcinomas induced in
    mice by mutant EGF receptors found in human lung
    cancers respond to a tyrosine kinase inhibitor or
    to down-regulation of the receptors. Genes Dev.
    2006 Jun 120(11)1496-510
  • Potti A, Mukherjee S, Petersen R, Dressman HK,
    Bild A, Koontz J, et al. A genomic strategy to
    refine prognosis in early-stage non-small-cell
    lung cancer. N Engl J Med. 2006 Aug