转移的结肠癌的全身治疗ppt课件.ppt

Chemotherapy for Metastatic Colon Cancer Scott Berry Sunnybrook Health Sciences Centre Where Were We Until 2000? N H HN O O F 5-FU FOLFOX FOLFIRI IFL bevacizumab cetuximab PTK 787 Capecitabine Panitumumab OS for 1st line Combinations 5-FU/LV (Saltz) 5-FU/LV (Douillard) 5-FU/LV (de Gramont) IFL (Goldberg) IFL (Saltz) FOLFIRI (Douillard) FOLFOX (de Gramont) FOLFOX (Goldberg) IFL+ Bevacizumab 0 5 10 15 20 25 Median OS (months) Overview/Objectives Review key evidence from randomized trials evaluating the chemotherapies and chemotherapy strategies that have emerged for metastatic colorectal cancer looking at both: Efficacy Safety Key Strategies and Questions: Which doublet should be used? ? Should we be using triplet therapy Can capecitabine replace infusional 5FU in doublets? Can sequential monotherapy replace initial doublet therapy? Can toxicity be reduced and efficacy maintained with “on/off” chemotherpay strategies? Chemotherapy Case 50 yo woman with no history of medical problems presents with bilobar liver and bilateral lung metastases ECOG 1 – some RUQ pain and cough What is the optimal chemotherapy choice for her? CAPECITABINE FOLFOX FOLFIRI CAPE IRI CAPE OX FOLFOXIRI Efficacy of Chemotherapy in First-Line CRC: Phase III Trial Results Saltz et al. N Engl J Med. 2000;343:905; Douillard et al. Lancet. 2000;355:1041;de Gramont et al. J Clin Oncol. 2000;18:2938 Regimen RR (%) Median OS (mo) 5-FU/LV IFL (Saltz trial) 21 39 (P0.001) 12.6 14.8 (P=0.04) 5-FU/LV FOLFIRI (Douillard trial) 22 35 (P0.005) 14.1 17.4 (P=0.031) 5-FU/LV FOLFOX4 (de Gramont trial) 22 51 (P=0.0001) 14.7 16.2 (P=0.12) CAPECITABINE FOLFOX FOLFIRI CAPE IRI CAPE OX FOLFOXIRI Phase III Intergroup N9741 Study(Goldberg JCO, 2004) R A N D O M I Z A T I O N Irinotecan + Oxaliplatin IFL FOLFOX 4 Phase II Sequential, Randomized CrossoverStudy Tournigand et al JCO 2004 FOLFIRI FOLFOX 6 N9741/Tournigand Trial: Results N9741 Tournigand IFL FOLFOX P-value FOLFIRI FOLF