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Objective: We designed this trial to investigate if modifications in levels of circulating vascular endothelial growth factor (VEGF) may be related to clinical response and outcome in advanced colorectal cancer patients during treatment with a weekly combination of cetuximab plus irinotecan. Methods: A total of 45 heavily pretreated metastatic colorectal cancer patients were prospectively evaluated for circulating levels of VEGF during the treatment with cetuximab plus weekly irinotecan. VEGF circulating levels were assessed at the following time points: just before and at 1, 21, 50 and 92 days after the start of cetuximab plus irinotecan treatment. Results: Basal VEGF median levels were significantly decreased just 1 day after the first anticancer infusion (p = 0.016) and reached the highest statistical significance 92 days after the first infusion (p < 0.0001). A total of 22 patients showed a reduction in median VEGF circulating levels of at least 50% 92 days after the first infusion with respect to the basal time point. For patients with at least a 50% reduction in VEGF levels, the response rate was 45.5% compared with 8.7% in the nonreduced VEGF group (p = 0.014). The median time to progression was 6 months in the reduced VEGF group versus 3.9 months in the other patients (p < 0.0001). In addition, overall survival was longer in patients with VEGF reduction (11.0 months) than in patients without (9.6 months; p = 0.01). Conclusion: These data represent the first evidence that suggests a role of VEGF reduction in the prediction of efficacy of treatment with cetuximab plus weekly irinotecan in heavily pretreated advanced colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients. Methods: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study. Treatment: Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1–14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well. Results: Most frequent related G3–4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3–4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0–15.7 months), the median response duration 2.8 months (95% confidence interval 1.2–5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7–6.3 months). The 1-year survival rate was 53.8%. Conclusions: The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]