Colon Cancer Hs 2009

COLON CANCER DR.DIVYESH G MEHTA MD

GOOD NEWS

2008 NEW CASES • • • • • • • • •

Male Prostate 186,320 (25%) Lung & bronchus 114,690 (15%) Colon & rectum 77,250 (10%) Urinary bladder 51,230 (7%)

• • • • • • • • •

Female Breast 182,460 (26%) Lung & bronchus 100,330 (14%) Colon & rectum 71,560 (10%) Uterine corpus 40,100 (6%)

2008 DEATHS • • • • • • • • • • •

Male Lung & bronchus 90,810 (31%) Prostate 28,660 (10%) Colon & rectum 24,260 (8%) Pancreas 17,500 (6%) Liver & intrahepatic bile duct 12,570 (4%)

• • • • • • • • • • •

Female Lung & bronchus 71,030 (26%) Breast 40,480 (15%) Colon & rectum 25,700 (9%) Pancreas 16,790 (6%) Ovary 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

LESIONS • MORE AA MALES • REL TO TYPE II DIABETIS AND IGF?

• JEWS FORM

EUROPE VS AFRICA IN ISRAEL

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 Angiogeni c 1-2 mm

Switch

Small tumor

• Nonvascular • “Dormant” Griffioen and Molema. Pharmacol Rev. 2000;52:237.

Larger tumor

• Vascular • Metastatic potential

VEGF: A Key Mediator of Angiogenesis Environmental Genes involved in factors1

tumorigenesis1,3

(hypoxia, pH)

Growth factors, hormones1

VEGF

(EGF, bFGF, PDGF, IGF-1, IL-1α , IL-6, estrogen)

Endothelial cell activation2

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

(p53, p73, vHL, src, ras, bcr-abl)

Binding and activation of VEGF receptor2 P P

P P

Surviva Proliferation Migration l

ANGIOGENESIS

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!