Colorectal cancer hassan ebrahim

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Updates on Colorectal Cancer Treatment: 

Hassan M Ebrahim , MD, MB CHB American Board Certified Doctors for Egypt Ahmed Maher Hospital – May 21, 2011 Updates on Colorectal Cancer Treatment

Introduction : 

More in middle-aged group > 50 year-old Left-side dominant Change of stool character Early detection Right-side disease Young-aged group, familial Advanced disease Introduction

Management of Early Stages: 

Stage I, II, III Colon cancer Low anterior resection (LAR) Rectal cancer Abdominal perineal resection (APR) permanent colostomy Anal preserve induction CCRT  surgery Management of Early Stages

High-risk of recurrence: 

Stage IIB (T4), III(N+) Adjuvant chemotherapy Attempt to eradicate micrometastasis Adjuvant CCRT – for rectal cancer To improve local control High-risk of recurrence

Adjuvant chemotherapy: 

Adjuvant chemotherapy No adjuvant C/T Adjuvant C/T DFS: 30% DFS: 50% 30% alive 50% alive 50% dead 70% dead Benefit 20% pts

Adjuvant chemotherapy: 

Bolus 5FU/LV as a standard 6 months duration 5-year OS 66% Oxaliplatin / Irinotecan era doublet chemotherapy as the standard for metastatic disease how about doublet in adjuvant setting ? Adjuvant chemotherapy

PowerPoint Presentation: 

New England Journal of Medicine 2004 FOLFOX vs. infusional 5FU/LV

PowerPoint Presentation: 

Oxaliplatin + bolus 5FU/LV vs. 5FU/LV Journal of clinical oncology 2007

PowerPoint Presentation: 

IFL, 6m 5FU/LV, 6m JCO 2004; 22: 245s CALGB Stage III  OP Too toxic, mortality Early closure!! FOLFIRI, 6m LV5FU, 6m Stage III  OP No difference !! JCO 2005; 23: 246s ACCORD 2 Irinotecan + 5FU/LV

Adjuvant chemotherapy: 

Oxaliplatin + 5FU/LV could be a new standard Not yet Adjuvant chemotherapy

Adjuvant chemotherapy in Stage II Disease: 

Benefits remain Controversial. Not routinely recommended. Adjuvant chemotherapy for medically fit, high risk stage II disease. MMR testing is favored than Oncotype DX Adjuvant chemotherapy in Stage II Disease

Metastatic Disease: 

Essentially incurable Resection of metastasis could prolong survival liver lung “Continuum of care” rather than “Lines” of therapy. Metastatic Disease

Active agents : 

5-FU leucovorin Oxaliplatin Irinotecan Monoclonal antibodies Cetuximab (Erbitux) Bevacizumab (Avastin) Panitumumab (Vecitibix) Active agents

5-FU: 

Leucovorin enhances 5FU binding Infusional better than bolus Capecitabine may substitute HDFL 5-FU

Oxaliplatin: 

Derivative from Cisplatin Accumulative toxicity Neuropathy Oxaliplatin

Irinotecan : 

Plant alkaloid unpredictable acute toxicity Diarrhea Gene polymorphism – UGT1A1 Impaired bile metabolism No accumulated toxicity Irinotecan

Doublet is mainstay: 

Oxaliplatin + 5FU/LV  FOLFOX Irinotecan + 5FU/LV  FOLFIRI Doublet is mainstay

PowerPoint Presentation: 

Journal of Clinical Oncology 2004 FOLFIRI FOLFOX FOLFIRI FOLFOX RR: 4% RR: 15% RR: 56% RR: 54% 220 pts Overall Survival : 21.5m vs. 20.6m

Three drug combination: 

FOLFOXIRI vs. FOLFIRI Improved outcome RR: 66%, 41%, p=0.0002 PFS: 9.8m, 6.9m, p=0.0006 OS: 22.6m, 16.7m, p=0.032 Three drug combination Journal of Clinical Oncology 2007

Bevacizumab (Avastin®): 

Anti-VEGF Ab (vascular endothelial growth factor) Avascular tumour Angiogenic switch Vascularised tumour Tumour cell intravasation Seeding in distant organs Secondary angiogenesis Premalignant stage Malignant tumour Tumour growth Vascular invasion Dormant micrometastasis Overt metastasis Bevacizumab ( Avastin ® )

PowerPoint Presentation: 

Kaplan-Meier Estimates of Survival Hurwitz, H. et al. N Engl J Med 2004;350:2335-234

Bevacizumab (Avastin®): 

Side effects & contraindications Is it a standard first line? Not yet Continuation beyond progression? A trend but contravrsial Bevacizumab ( Avastin ® )

Cetuximab (Erbitux): 

Anti-EGFR Ab (Epidermal growth factor receptor) Monotherapy vs. combined with chemotherapy K-ras wild type First line (+ Irinotcan), second line or refractory Cetuximab ( Erbitux )

PowerPoint Presentation: 

Cetuximab Montherapy vs. Cetuximab plus Irinotecan Cunningham, D. et al. N Engl J Med 2004;351:337-345

PowerPoint Presentation: 

. Tabernero J et al. JCO2007;25:5225-5232 ©2007 by American Society of Clinical Oncology Cetuximab, Oxaliplatin,vs. Cetuximab plus Oxaliplatin

Panitumumab (Vectibix): 

Anti-EGFR Ab K-ras wild type First line, second line or refractory Less hypersensitivity reactions Are EGFR MoAbs interchangeable? Panitumumab ( Vectibix )

PowerPoint Presentation: 

. Van Cutsem E et al. JCO 2007;25:1658-1664 ©2007 by American Society of Clinical Oncology Panitumumab vs. Best Supportive Care

PowerPoint Presentation: 

K K K K signal transduction Migration Proliferation Adhesion Differentiation K K K 1 1 1 1 1 2 2 EGFR MoAbs K 1 K 1 K 1 K 1

Monoclonal Antibodies: 

Plus 5FU-based doublet is the mainstay mAbs optimal combination and sequence to be defined Monoclonal Antibodies