8th Annual Kidney Cancer Survivors Day

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8th Annual Kidney Cancer Survivors Day

• Dr. David Minor
• May 2, 2009

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California Kidney Cancer Foundation

• FOUNDED 1994 TO MAKE NEW AND ADVANCED FORMS OF
  THERAPY FOR KIDNEY CANCER AVAILABLE IN NORTHERN
  CALIFORNIA
• TO FACILITATE STATE-OF -THE-ART CARE FOR KIDNEY
  CANCER PATIENTS THROUGH EDUCATION, ADVOCACY, AND
  SUPPORT OF PATIENTS AND THEIR FAMILIES
• MULTIDISCIPLINARY APPROACH TO PATIENT CARE WITH
  CLINICAL RESEARCH USING IMMUNOTHERAPY AND
  TARGETED THERAPY

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Kidney Cancer

• Incidence 51,000 cases/year in U.S.
  12,800 deaths/year in U.S. 3 of
  all cancers
• Symptoms blood in urine, flank pain, fatigue,
  symptoms from metastases
• 30 of patients have distant metastases at
  diagnosis
• No screening tests available
• Diagnosis by CT scan-- accuracy 98 if
  symptomatic
• Cause--more common in men and in
  smokers, hypertension, overweight,?organic
  solvents

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Kidney Cancer Staging and 5-year Survival

• Stage 1 Tumor lt 7cm size
• Stage 2 Tumor gt7cm
• Stage 3 Tumor invades renal vein or adrenal
  gland or lymph nodes
• Stage 4 Distant metastases to lungs, bone,
  brain, etc.

• 95 5-year survival
• 88
• 59
• 20

Ref Cohen HT,McGovern FJ, N Eng J Med 2005
3532477-2490
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Renal Cell Cancer Pathology

• Clear Cell Renal Carcinoma 80 usually
  mutation of von Hipple-Lindau (VHL) gene,
• Papillary Renal Cell Cancer 15
• Chromophobe Renal Cancer 5
• Collecting Duct Carcinoma 1
• Different Grades and Sarcomatoid variants occur
  with above
• Cancer of the Renal Pelvis is usually
  transitional cell cancer similar to bladder cancer

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Kidney Cancer Surgery

• Early Stages-partial nephrectomy, laparoscopic
  nephrectomy options vs. classic nephrectomy
• Late Stages require radical nephrectomy, removal
  of tumor from vena cava, other organs
• Nephrectomy may benefit patients with stage 4
  metastatic disease
• Post-operative adjuvant trial sunitinib/sorafenib/
  placebo in progress
• Prior adjuvant therapies ineffective
• local radiation therapy
• alpha interferon
• gamma interferon
• High-dose Interleukin 2
• Oncophage vaccine

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Pathogenesis of RCC development and progression

• Von Hippel-Lindau syndrome is characterized by
  inherited mutation of VHL gene and development of
  RCC and other vascular tumors
• Sporadic non-inherited clear cell RCC has
  acquired VHL gene mutation or inactivation
• The normal function of the VHL gene product
  (pVHL) is helps destroy of HIFa inside cells
• Mutation of VHL in RCC leads to altered pVHL and
  increased HIFa
• HIFa expression leads to overexpression of
  hypoxia-inducible genes
• VEGF, PDGF,TGF overproduction promote tumor
  angiogenesis and proliferation (B.Rini)

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RCCTargets of Single Agents

HIF
Bevacizumab
Erlotinib
TGF-a
VEGF
PDGF
VEGFR
EGFR
PDGFR
Sunitinib, Sorafenib, AG-013736
Sorafenib
Sorafenib
RAF
RAF
Kaelin WG. Nat Rev Cancer. 20022673-682.
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KIDNEY CANCER THERAPY

• Stage 1a Surgery only
• Stage 1b, 2, or 3 Surgery /- adjuvant therapy
  trial
• Stage 4 or Recurrent Cancer- Nephrectomy first?
• Immunostimulants Interleukin-2
• Interferon alpha
• Targeted therapy Antiangiogenic Therapy
• Sorafenib(Nexavar)
• Sunitinib (Sutent)
• Bevacizumab (Avastin)
• Temsirolimus (Torisel)-mTOR inhibitor
• Everolimus (Afinitor) -mTOR inhibitor

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Clinical Trials What and Why

• Phase I, Phase II, Phase III-decreasing risk
• A biologic experiment with humans
• Access to a new therapy that may be better
• Access to expertise not available next door
• Closer monitoring of your cancer and of treatment
  side effects
• Choose a trial specifically for kidney cancer

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New Agents in Clinical Trials

• VEGF inhibitors
• Pazopanib (Glaxo)
  Axitinib(Pfizer) Vandetanib
  (Astra-Zenica) Vatalanib(Novartis) Afibercept
  - VEGF trap
• Immunotherapy Anti-CTLA- Ipilimumab Interl
  eukin-7
• Allogeneic Lymphocyte Infusions
• Others Ixabepilone Yttrium-90
  conjugated G250 antibody Vorinostat
• Desatinib

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Kidney Cancer Symposium and Survivors Day 2009

• William Bro - Kidney Cancer Association
• Dr . Andrea Harzstark - mTOR inhibitors
  temsirolimus and eveolimus
• Dr. Sandya Srinivas - Sorafenib and Sunitinib
• Dr. Stephen Schatz - Surgery and Local therapy
• Dr. Daniel Sze - Radioisotope embolization
• Dr. Julie Russell - Managing Side Effects of
  Target Therapy
• Felmir Singson - Living with Renal Cell Cancer
• Greta Macaire - Nutrition and Cancer
• Milena Fiore - Integrative Medical Therapies
• Dr. David Minor - Immunotherapy and Future
  Therapy