Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

Contains fulltext : 79995.pdf (publisher's version ) (Open Access)BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.

Positron emission tomography using 2-deoxy-2-[18 F]-fluoro-D-glucose for response monitoring in locally advanced gastroesophageal cancer; a comparison of different analytical methods

Purpose: To determine the ability of 2-deoxy-2-[18F] -fluoro-D-glucose (FDG) positron emission tomography (PET) to monitor response in locally advanced gastroesophageal cancer (LAGEC). Additionally, optimal FDG-PET methods for response monitoring were selected. Procedures: Sequential dynamic FDG-PET scans were performed in 13 patients with LAGEC (T2-3N0-1M0-1a) treated with neoadjuvant cisplatin and gemcitabine plus granulocyte macrophage colony stimulating growth factor at a three weekly schedule. The standard FDG-PET method, nonlinear regression (NLR), was compared with computed tomography (CT), endoscopic-ultrasound (EUS), and histopathology as well as with 21 simplified analytical FDG-PET methods. Results: Five out of 12 operated tumors responded histopathologically with less than 10% residual tumorcells (42%). These had a higher decrease in FDG uptake compared with nonresponders (P = 0.008). Early (after two cycles) and late (after completed induction therapy) response evaluation showed a specificity of 86% and 100%, respectively, and a sensitivity of 100%. Both FDG-PET and EUS were superior to CT. From 21 methods analyzing FDG uptake, the quantitative Patlak analysis, the simplified kinetic method (SKM), and the semiquantitative standardized uptake value corrected for bodyweight (SUV-BW) seemed to correlate best with NLR. Conclusions: FDG-PET reliably predicted response in LAGEC. FDG-PET measurements using Patlak analysis or the more clinical applicable SKM and SUV-BW were acceptable alternatives to NLR