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Adjuvant and neo-adjuvant therapies for RCC

Adjuvant and neo-adjuvant therapies for RCC. Dr. Camillo Porta S.C. di Oncologia Medica I.R.C.C.S. Policlinico San Matteo , Pavia. Back to the basics : terminology. Adjuvant therapy:

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Adjuvant and neo-adjuvant therapies for RCC

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  1. Adjuvant and neo-adjuvant therapies for RCC Dr. Camillo Porta S.C. di OncologiaMedica I.R.C.C.S. Policlinico San Matteo, Pavia

  2. Back to the basics: terminology • Adjuvant therapy: • Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back • Neo-adjuvant therapy: • Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given NCI Dictionary of Cancer Terms

  3. Adjuvant therapy

  4. The natural history of RCC • Presentation at diagnosis1: • 45% with localized disease • 25% with locally advanced disease • 20–30% metastatic disease • 33% of patients treated for localized disease will develop metastatic disease2 1. National Cancer Institute. SEER cancer statistics fact sheet: cancer of the kidney and renal pelvis. Accessed 2009; 2. Flanigan RC et al. Curr Treat Options Oncol 2003;4:385–90.

  5. Completed RCTs of adjuvant Tx

  6. Completed RCTs of adjuvant Tx

  7. Meta-analysis of RCTs of adjuvant Tx Massari F, et al. Clin Genitourin Cancer 2013 (E-pub ahead of print)

  8. Ongoing RCTs of targeted agents as adjuvant Tx

  9. Adjuvant Tx for RCC: conclusions • To date, no treatment emerged as a standard of care in this setting • Presently, patients should be thus offered just obser-vation • Enrollment into well-desigend and adequately con-ducted RCTs is mandatory

  10. Neo-adjuvant therapy

  11. Neo-adjuvant Tx: pros and cons

  12. Are we able to achieve tumor shrinkage? Sorafenib treatment Escudier B, et al. ECCO 13 – the European Cancer Conference, Paris, October 30-November 3, 2005; abs.794.

  13. Are we able to achieve tumor shrinkage? Sunitinib treatment (4 cycles) Level I thrombus Level II thrombus Shuch B, et al. BJU Int 2008;102:692-696

  14. Are we able to achieve tumor shrinkage? 8 Weeks of therapy Baseline Bevacizumab treatment Jonasch E, et al. J Clin Oncol 2009;27:4076-81

  15. How much tumor shrinkage are we really able to achieve? Van der Veldt AAM, et al. Clin Cancer Res 2008;14:2431-6; Thomas AA, et al. J Urol 2009;181:518-23; Jonasch E, et al. J Clin Oncol 2009;27:4076-81

  16. Are there risks with such an approach? CG Wood, personal communication

  17. Are there risks with such an approach? CG Wood, personal communication

  18. Are there risks with such an approach? CG Wood, personal communication

  19. Are there risks with such an approach? CG Wood, personal communication • *Adjusted for: • Pre-operative albumin • Smoking status (never, current, former) • Pre-operative hemoglobin • Laparoscopic vs open surgery • ECOG performance status • Body mass index • Age

  20. How to deal with these issues? Stages of wound healing II. cell proliferationand matrix deposition Consider drug half-life Temsirolimus: 17 hrs Sorafenib: 24-48 hrs Sunitinib: 60-110 hrs Bevacizumab: 14-21 days Pazopanib: 30.9 hrs I. inflammation III. matrix remodelling • Fibroplasia • Angiogenesis • Re-epithelization • Extracelluar matrix sythesis • Collagens • Fibronectin • Proteoglicans Maximum response • Granulocytes • Phagocytosis Extracellular matrixsynthesis, degradationand remodelling  Tensile strength  Cellularity  Vascularity • Bleeding • Coagulation • Platelet activation • Complement activation Withheld treatment for at least 2 or 3 half-lives before and after surgery • Macrophages • Cytokines Days after wounding (log scale)

  21. Prognostic factors for Sunitinib: nihil novo sub solem • Present, initial, body of evidence would suggest that significant primary tumor downstaging will not be realized with the current generation of targeted therapy agents CG Wood, personal communication

  22. Thank You for Your kind attention!!! c.porta@smatteo.pv.it

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