1. Regional Perspectives on Renal Cell Carcinoma Mohamed Abdulla M.D. Professor of Clinical Oncology Cairo University AfME. September 17 th 2010W: www.oncologyclinic.org E: mohamed.abdulla@oncologyclinic.org

3. Objectives & Agenda: Available epidemiological data. Molecular events & therapeutic options. What we need as a future perspective.

4. Increasing Incidence: Pantuck, AJ, et al. J Urology 2001; 166:1612

5. Globocan 2010 (v1.1): Incidence (ASR): 3.9/100000 Mortality: 1.6/100000

6. Globocan 2010 (v1.1):

8. Incidence ASR/100000: 1.6 Mortality/100000:1.3 Incidence ASR/100000: 1.1 Mortality/100000: 0.9 Incidence ASR/100000: 1.2 Mortality/100000: 0.9 Incidence ASR/100000: 0.6 Mortality/100000: 0.5 Globocan 2010 (v1.1):

10. First Look Impression Low Numbers, National Cancer Registries. High Mortality Among Diagnosed Patients We need to improve our performance…

11. To Emphasize Urologist Medical Oncologist EUANCCN

12. Management of Stage IV RCC: 1. The Blackout Story: TreatmentOORImpact on PFS &OS Chemo/Immunoth- erapy 10 – 30%Not Demonstrated Chemotherapy0 – 10%Non Hormonal Therapy0 – 10%Non Mignogna et al. BMC Cancer 2006;6:293

13. Management of Stage IV RCC: 2. Immunogenic Tumor: TreatmentOORImpact on PFS &OS IFN - Alpha12 – 20%Superior to Cth. SC IL-2 Alone12 – 20%Not Demonstrated SC IL – 2 + IFN @20 – 30%Not Demonstrated High Dose IV IL-215 – 25%OS benefit only if CR 3 – 10% Chemo/Immunoth- erapy 10 – 30%Not Demonstrated Cochrane Review 2005: IFN provides a modest survival benefit (12.5%) compared to others. IL-2 has not been sufficiently validated in RCT. Unsatisfactory Results

14. Management of Stage IV RCC: 3. From Histology to Molecular Biology: BHD=Birt-Hogg-Dubé, FH=fumarate hydratase, VHL=von Hippel-Lindau. Modified from Linehan WM et al. J Urol. 2003;170:2163-2172. RCC Clear cell 75% Type Incidence (%) Associated mutations VHL Papillary type 1 5% c-Met Papillary type 2 10% FH Chromophobe 5% BHD Oncocytoma 5% BHD

15. Management of RCC: 3. From Histology to Molecular Biology & Possible Targets for Treatment: HIF = VEGFREGFR PDGFR Sunitinib, Sorafenib, AG-013736 Sorafenib Bevacizumab RAF Erlotinib Kaelin WG. Nat Rev Cancer. 2002;2:673-682. VEGF TGF-a PDGF RAF Sorafenib Temsorilimus Everolimus pVHL

16. Management of RCC: 3. From Histology to Molecular Biology & Possible Targets for Treatment: 1992 - 2005 2006 200720082009 INF – Alpha HD IL-2 Sorafinib Sunitinib TemsorilimusEverolimus Bevacizumab + INF-Alpha Pazopanib Axitinib

17. NCCN Practice Guidelines v.2.2010 RCC Stage I,II,III Surgery Stage IV or Recurrent and/ or Metastatic Resectable Single Metastasis Resectable 1ry with Multiple Metastases Unresectable Follow up or Clinical Trial Nephrectomy + Metastatectomy Nephrectomy in Selected Pts First Line Therapy

18. NCCN Practice Guidelines v.2.2010 Stage IV Relapsed Unresectable Clear Cell Clinical Trial Sunitinib Temsorilimus Pazopanib HD IL2 Sorafinib BSC Non-Clear Cell Clinical Trial Temsorilimus Sorafinib Sunitinib Pazopanib Cth. BSC

19. Subsequent Therapy (2 nd Line): Clinical Trial. Everolimus; after TKI. Sorafinib; after Cytokine Therapy. Sunitinib; after Cytokine Therapy. Pazopanib; after Cytokine Therapy. BSC. NCCN Practice Guidelines v.2.2010

20. What we need as a future Perspective? 1.Emphasize the need for national cancer registries in the region. 2.National awareness to detect cases as early as possible; health care professionals & general population. 3.Ensure treatment within a strict protocol & according to guidelines; (CME). 4.……..

21. I t is never true that nothing more can be done.