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J C Nunes Marques Serviço de Oncologia Médica Centro Hospitalar de Lisboa Ocidental

Sequential Therapy in Renal Cell Carcinoma. J C Nunes Marques Serviço de Oncologia Médica Centro Hospitalar de Lisboa Ocidental. Molecular Pathways and Targeted Therapies in Renal-Cell Carcinoma. Brugarolas J. N Engl J Med 2007;356:185-187. Angiogenesis: a target for anticancer therapy.

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J C Nunes Marques Serviço de Oncologia Médica Centro Hospitalar de Lisboa Ocidental

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  1. Sequential Therapy in Renal Cell Carcinoma J C Nunes Marques Serviço de Oncologia Médica Centro Hospitalar de Lisboa Ocidental

  2. Molecular Pathways and Targeted Therapies in Renal-Cell Carcinoma. Brugarolas J. N Engl J Med 2007;356:185-187.

  3. Angiogenesis: a target for anticancer therapy Rini. Clin Cancer Res 2007, 13 Faivre et al. Nat Ver Drug Disc 2007, 6 Homsi and Dand. Cancer control 2007, 14 Andrae et al. Genes Dev 2008, 22 Kerbel. N Engl J Med 2008, 358 Sonpavde et al. Expert Opin Investig Drugs 2008, 17 Ma and Adjei. CA Cancer J Clin 2009, 59

  4. Chronology and uses of available molecular-targeted agents in metastatic renal cell carcinoma in the U.S. and Europe. Hutson T E The Oncologist 2011;16:14-22

  5. Ongoing Phase III Trial: Pazopanib vs Sunitinib in the first-line treatment of patients with mRCC (COMPARZ) US National Institutes of Health Web Site http://www.clinicaltrials.gov/ct2/show/NCT00720941 acessed26oct2011

  6. Potencial Biomarkers in mRCC

  7. Escudier B, et al. Cancer 2009; 115 (10 Suppl): 2321-2326 1 Escudier et al. NEngJMed 2007; 356 2 Motzer et al. NEngJMed 2007; 356 4 Escudier et al. Lancet 2007; 370 10 Rixe et al. Lancet Oncol 2007; 8 12 Scharzberg et al. J Clin Oncol 2008; 26 13 Rini BI et al. J Clin Oncol 2008; 26 14 Rini BI et al. J Clin Oncol 2007; 25 15Sablin MP et al. J Clin Oncol 2007; 25

  8. Rational of sequential therapy • each targeted agent possesses a unique biologic profile • patients have benefited from subsequent therapy with a different antiangiogenic agent • full dose of each drug can be delivered without overlapping toxicities • additional PFS benefit can been achieved • the aim of therapy is to maximize the overall benefit to patient in terms of both quality and duration of life Sablin MP, et al. J Clin Oncol. 2007;25 (18S): Abstract 5038 Dham A, et al. J Clin Oncol. 2007;25(18S):Abstract 5106 Drabkin HÁ, et al. J Clin Oncol.2007;25(18S):Abstract 5041

  9. *available at http://clinicaltrials.gov

  10. Summary • Thesequentialapproachwithtargetedagentshaverevealedclinicalefficacy • Data suggeststhatthereisonlynegligibilecross-resistancebetweenTKIs • Inclinicalstudiesofsequentialtherapy, everolimuswaseffectiveaftertreatmentwithoneortwoTKIs • Inclinicalstudiesofsequentialtherapy, sequentialtreatmentwastolerableandtoxicitywaspredictable

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