Biotechnology Healthcare - June 2008 - (Page 33) FIGURE 3 Survival benefit of bevacizumab plus first-line chemotherapy relative to other treatment strategies in patients with metastatic colorectal cancer ? 24 20–21 21 20–21 20–21 Progression-free survival >50% Second-line irinotecan >50% Second-line oxaliplatin >50% Receives all third-cytotoxic 17 16 14–15 14–15 12–13 12–13 Median overall survival (months) 18 15 12 9 4–6 6 3 0 Bevacizumab plus FOLFOX or FOLFIRI or XELOX then unused cytotoxics Anti-VEGF with sequential combination chemotherapy Bevacizumab plus IFL FOLFIRI then oxaliplatin FOLFOX then irinotecan FOLFIRI FOLFOX IFL Infusional 5-FU/LV Capecitabine Bolus 5-FU/LV BSC Anti-VEGF with combination chemotherapy Sequential combination chemotherapy Combination chemotherapy 5-FU/LV monotherapy No chemotherapy Under investigation BSC=best supportive care; FOLFIRI=fluorouracil/leucovorin plus irinotecan; FOLFOX=every two weeks chemotherapy regimen combining bolus with infusional fluorouracil/leucovorin plus oxaliplatin; FU/LV=fluorouracil/leucovorin; IFL=bolus fluorouracil/leucovorin plus irinotecan; VEGF=vascular endothelial growth factor; XELOX=capecitabine plus oxaliplatin. Source: Venook 2005; reprinted with permission (Yu 2007). Although response rate may be an appropriate tool to identify agents for continued evaluation, it is probably inappropriate for determining efficacy for drug approval (Michaelis 2006). Colorectal cancer is the thirdleading cause of cancer-related deaths and, in terms of incidence, is the third most common cancer (ACS 2008). If found early enough, surgery is the primary treatment and often results in a cure. According to the Cancer Trends Progress Report on Colorectal Cancer (NCI 2005), when the condition is metastatic, the recommended treatment is adjuvant chemotherapy. Unfortunately, mortality still remains high with advanced metastatic colorectal cancer (Ries 2000), but recent research shows that the addition of an epidermal growth factor receptor inhibitor to chemotherapy can be helpful (Van Cutsem 2006). Meyerhardt (2006) studied the efficacy of cetuximab (Erbitux) therapy in 24 patients with metasta- tic colorectal cancer previously treated with either gefitinib (Iressa) or erlotinib (Tarceva) and standard chemotherapy. None of the patients had a partial or CR as defined by the trial protocols, but 72 percent had stable disease, and progression-free survival (PFS) was 5.1 months for all patients. Those patients who had documented disease progression while receiving either gefitinib or erlotinib had 6 months of PFS (Meyerhardt 2006). Although cetuximab is more MAY/JUNE 2008 · BIOTECHNOLOGY HEALTHCARE 33
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