COLON CANCER

DR.DIVYESH G MEHTA MD
GOOD NEWS
2008 NEW CASES
• Male • Female
• Prostate • Breast
• 186,320 (25%) • 182,460 (26%)
• Lung & bronchus • Lung & bronchus
• 114,690 (15%) • 100,330 (14%)
• Colon & rectum • Colon & rectum
• 77,250 (10%) • 71,560 (10%)
• Urinary bladder • Uterine corpus
• 51,230 (7%) • 40,100 (6%)
2008 DEATHS
• Male • Female
• Lung & bronchus • Lung & bronchus
• 90,810 (31%) • 71,030 (26%)
• Prostate • Breast
• 28,660 (10%) • 40,480 (15%)
• Colon & rectum • Colon & rectum
• 24,260 (8%) • 25,700 (9%)
• Pancreas • Pancreas
• 17,500 (6%) • 16,790 (6%)
• Liver & intrahepatic bile duct • Ovary
• 12,570 (4%) • 15,520 (6%)
WHO ARE AT RISK?
SPORADIC OR INHERITED?
RISK FACTORS

• RED MEAT
• OBESITY
• LACK OF EXERCISE
• LACK OF FRUITS AND VEGGIES
• EXCESS ALCOHOL INTAKE
• CALCIUM?,FOLIC ACID?,COXII INH
RISK FACTORS

• INFLAMMATORY BOWEL DISEASES

• URETEROCOLOSTOMY
THERE ARE CHANGES AFOOT

• LEFT TO RIGHT • JEWS FORM EUROPE

LESIONS VS AFRICA IN ISRAEL
• MORE AA MALES
• REL TO TYPE II
DIABETIS AND IGF?
FAMILY HISTORY

• POLYPOSIS(FAP)
• FAMILIAL NON POLYPOSIS
• TURCOT’S SYNDROME
• LYNCH SYNDROMES
• GARDENER’S SYNDROME
FAMILIAL COLON CA
FAP
• 1 to 2 % INCIDENCE
• APC GENE
• AD,100% PENETRANCE
• RX:SCREENING,COLECTOMY,CELECOXIB(40% RED)
HNPCC GENE(LYNCH SY)
• 5 TO 6 % INCIDENCE
• AD,80% PENETRANCE
• 3 FAM MEMBERS +,TWO GEN,ONE<50
• LYNCHII :OVARIAN,BREAST,ENDO,BILIARY CA
SCREENING

• REDUCES CANCER BY REMOVING

PREMALIGNANT LESIONS AND POLYPS
• PREVENTABLE AND CURABLE CANCER!
12 NODES MIN
CHEMOTHERAPY
ADJUVANT TO SURGERY

• PREVENTS
RECURRENCE
• NODE POS DISEASE
• STAGE 2 IN SPECIAL
CIRCUMSTANCES
• OVER 20 YEARS
EXPERIENCE
RECTAL CARCINOMA

• UPFRONT CHEMOXRT
COLON CA

• ADJUVANT RX TO ERADICATE
MICROMETS AND LEAD TO CURE
ADJUVANT

• FU/LEVAMISOLE(JAMA 9/90)
• FU/LEUKOVORIN
• FOLFOX
• XELODA
• FOLFIRI /IRINOTECAN NOT APPROVED
12 NODES MIN
Advanced Disease
• CHEMO
FU/LEUKOVORIN
FOLFOX
FOLFIRI
AVASTIN
ERBITUX
VECTIBIX
• RADIATION
• PAIN CONTROL
• NUTRITION
Chemo drugs

• 5FU
• LEVAMISOLE
• LEUKOVORIN
• XELODA
• OXALIPLATIN
• CAMPTOSAR
• NEW AGENTS
NEW AGENTS

• ANTIANGIOGENESIS
BEVACIZUMAB IN METASTATIC CA
• EGFR BLOCKADE
CETUXIMAB
• PAN HR BLOCKADE
PANITUMUMAB
 Vasculature and Tumor Growth

Angiogenic

1-2 mm Switch

Small tumor Larger tumor

• Nonvascular • Vascular
• “Dormant” • Metastatic potential

Griffioen and Molema. Pharmacol Rev. 2000;52:237.

 VEGF: A Key Mediator of
Angiogenesis
Environmental factors 1
Genes involved in
(hypoxia, pH)
tumorigenesis1,3
Growth factors, (p53, p73, vHL, src, ras,
hormones1 VEGF bcr-abl)
(EGF, bFGF, PDGF,
IGF-1, IL-1, IL-6, estrogen)
Binding and activation
of VEGF receptor2

P P
Endothelial cell P P
activation2
Survival Proliferation Migration

ANGIOGENESIS
Dvorak. J Clin Oncol. 2002;20:4368.
Ferrara et al. Nat Med. 2003;9:669.
Ebos et al. Mol Cancer Res. 2002;1:89.
CETUXIMAB(ERBITUX)

• APPROVED FOR METASTATIC CRC

• SAFE
• SKIN RASH AS MARKER FOR RESPONSE
• BLOCKS EGFR
• GOOD ALONE,GOOD IN COMBINATION
PANHER BLOCKER

• PAMITUMUMAB
• HUMAN MAB
• RASH MAJOR SIDE EFFECT
• PAM VS SC ONLY TRIAL SO FAR
Estimated Drug Costs for Eight Weeks of Treatment for Metastatic Colorectal Cancer

Schrag, D. N Engl J Med 2004;351:317-319

PROGRESS IN MCRC

Median Survival
INCREASE
FROM 6 MONTHS
TO 28 MONTHS
COST $1000
TO $250000
PER PATIENT!