sformed Despite the improvement in median overall survival (mOS) over the last 10 years, metastatic colorectal cancer (mCRC) remains a major public health problem accounting for 8% of cancer deaths in adults in the western world. Combination chemotherapy with granisetron infusional 5-fluorouracil (FU) and folinic acid (FA) with either irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) is commonly used in the daily practice. Expansion of mOS and 5-year survival rate have been correlated with the proportion of patients receiving all active chemotherapeutic agents and the increasing use of hepatic or/and pulmonary resection of metastatic lesions.

The addition of bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), to combination chemotherapy in the first-line setting appears to Triciribine increase the efficacy of systemic treatment in randomised trial, but the magnitude of the benefit is debatable. However, one can argue that the benefit from addition of Bev to irinotecan-based chemotherapy is generally greater than that observed when it is combined with oxaliplatin-based regimens. Capecitabine, an oral fluoropyrimidine, was designed to mimic continuous infusion 5-FU and to generate 5-FU preferentially in the tumour tissue. Capecitabine has similar efficacy compared with 5-FU/LV as first-line treatment in mCRC patients; the advantage of capecitabine is its convenient oral administration.

Capecitabine in combination with oxaliplatin (CAPOX) has consistently demonstrated purchase asenapine similar efficacy results compared with the FOLFOX regimen. Likewise, the combination of capecitabine with irinotecan (CAPIRI) was proven effective and safe in a large randomised trial. Finally, the combination of Bev and capecitabine has a synergistic effect, in an in vivo xenograft model, with a greater duration of tumour growth inhibition than with either agent alone. Based on these data, the Hellenic Oncology Research Group (HORG) designed a randomised phase-II trial in order to investigate the efficacy and safety of addition of Bev to FOLFIRI or CAPIRI as front-line treatment of patients with mCRC.The study was approved by the Ethics and Scientific Committees of each participating centre and all patients gave written informed consent prior to study enrolment.The 5-FU or capecitabine dose was reduced in case of grade-3–4 stomatitis or dermatitis. Bevacizumab was permanently discontinued in patients developing gastrointestinal perforation, wound dehiscence requiring medical intervention, serious bleeding, nephrotic syndrome or hypertensive crisis.

Temporary discontinuation of Bev administration was implemented in patients with order asenapine evidence of moderate-to-severe proteinuria and in patients with severe hypertension that was not controlled with medical management. The primary endpoint of the study was PFS. Secondary endpoints were mOS, response to treatment and safety profile in terms of adverse events incidence, dose reductions and treatment delays. Based on the results of the BICC trial the study was designed in order to detect a 3-month difference in PFS with an 80% power at a significance level of 0.05. In order to achieve the statistical hypothesis, 165 patients (per arm) should be enrolled in 36 months, with an additional follow-up period of 24 months.