AIM:To evaluate the combination of bevacizumab with infusional 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan (FOLFIRI) in patients with advanced colorectal cancer (CRC) pretreated with combination regimens including irinotecan and oxaliplatin.
METHODS:F o u r t e e n p a t i e n t s ( m e d i a n a g e 5 6 years) with advanced CRC, all having progressed after oxaliplatin-and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m 2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m 2 followed by a bolus of 5-FU 400 mg/m 2 and then 22 h continuous infusion of 600 mg/m 2 given on two consecutive days every 14 d.
RESULTS:The median number of cycles of chemotherapy was six (range 3-12). The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo (95% CI 2.0-8.7), and the median overall survival was 10.9 mo (95% CI 9.6-12.1). Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles.
CONCLUSION:Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC. www.wjgnet.com regimens [21] . In a phase 2 trial of treatment of CRC, the addition of bevacizumab to FU/LV increased the response rate, the median time to disease progression, and the median duration of survival [22] . Recently, it has been shown in randomized phase Ⅲ trials that bevacizumab, when combined with irinotecan plus bolus FU/LV in the firstline treatment of metastatic CRC, and with oxaliplatin plus continuous FU/LV (FOLFOX) in second-line treatment leads to an increased median survival, progression-free survival (PFS), and response rate compared with cytotoxic chemotherapy alone [23,24] . The goal of this trial was to evaluate the safety and activity of bevacizumab plus LV, 5-FU and irinotecan (FOLFIRI) in patients with advanced CRC that had progressed after treatment with both irinotecan-and oxaliplatin-based chemotherapy regimens.
MATERIALS AND METHODS
Eligibility criteriaThe eligibility criteria were as follows: histologically confir med CRC (adenocarcinoma), bidimensionally measurable disease, no secondary malignancy, age > 18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, and a life expectancy of > 3 mo. Adequate hematological, hepatic and renal function (including urinary excretion of no more than 500 mg protein/d) were also required. Patients should have had and failed both oxaliplatin-and irinotecan-based treatment prior to enrolment. Failure due to significant intolerance to either drug was allowed.Exclusion criteria included thromboembolism that required thera...
