of patients /th th align=”center” valign=”top” charoff=”50″ rowspan=”1″ colspan=”1″ % /th th align=”center” valign=”top” charoff=”50″ rowspan=”1″ colspan=”1″ em P /em -value /th /thead Any12876122720.41LOHP-based1046298590.39Irinotecan-based241424140.98Bevacizumab392338230.98Cetuximab503850300.24 Open in a separate window Discussion Addition of monoclonal Asarinin antibodies targeting either VEGF or EGFR to irinotecanC5-FU/FA combination chemotherapy in some studies has demonstrated an increase in RR, PFS and mOS compared with chemotherapy alone (Hurwitz em et al /em , 2004; Van em et al /em , 2009). written informed consent prior to study enrolment. Treatment protocol Patients were randomised to receive either FOLFIRI-Bev (Arm-A: irinotecan at the dose of 180?mg?m?2, iv, on day 1; FA at the dose of 200?mg?m?2, iv, on days 1 and 2; and 5-FU at the dose of 400?mg?m?2day?1, iv, bolus and 600?mg?m?2?day?1, as a 22-h iv continuous infusion, on days 1 and 2, plus 5?mg?kg?1 Bev on day 1, every 2 weeks) or CAPIRI-Bev (Arm-B: capecitabine at the dose of 2000?mg?m?2, p.o., on days 1C14; irinotecan at the dose of 250?mg?m?2, iv, on day 1; and Bev at the dose of 7.5?mg?kg?1, iv, every 3 weeks). Stratification factors were age (?65 years 65 years), extent of metastatic disease (liver limited other) and prior adjuvant chemotherapy (yes no). Routine antiemetic prophylaxis with a 5-hydroxytryptamine-3-receptor antagonist was used in both arms. Treatment was administered until disease progression or unacceptable toxicity, or consent withdrawal. Patients were assessed for toxicity before each cycle using the National Cancer Institute Common Toxicity Criteria version 3.0. Chemotherapy was delayed until recovery if neutrophils were less than 1.5 109/l or platelets TMEM8 less than 100 109/l, or for significant (more than grade-II) persisting non-haematologic toxicity. Doses of all drugs were reduced by 15% in subsequent cycles in case of grade-4 neutropenia or grade-3C4 thrombocytopenia lasting for more than 3 days, or in case of febrile neutropenia. No prophylactic administration of granulocyte colony-stimulating factor was allowed. Doses of irinotecan and 5-FU or capecitabine were reduced by 15% in subsequent cycles in case of grade-3 or 4 diarrhoea. The 5-FU or capecitabine dose was reduced in case of grade-3C4 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 evidence of moderate-to-severe proteinuria and in patients with severe hypertension that was not controlled with medical management. Patient evaluation Pre-treatment evaluation included medical history and physical examination, complete blood cell count (CBC) with differential and platelet count, blood chemistry, serum levels of Asarinin carcinoembryonic antigen, and computed tomographic (CT) scans of the chest and imaging of the abdomen (CT or MRI). Pre-treatment evaluation had to be performed within 2 weeks prior to study entry. During treatment, a CBC with was performed weekly. In addition, patients were clinically assessed and blood chemistry was performed before each treatment cycle. Response to treatment was evaluated every 8 weeks according to the RECIST criteria (Therasse 11 months) Asarinin 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. The KaplanCMeier method was used to estimate PFS and survival curves, and log-rank test was used to compare curves. Cox proportional hazards modelling was used to calculate hazard ratios (HRs) and confidence intervals (CIs). Heterogeneity tests were performed in order to determine whether the effect size for the subgroups varies significantly from the main effect. Forest plots were used in order to investigate the effect of the studied variables apart in accordance to the overall effect for each case. em /em 2-Tests were used to compare toxicity and confirmed response rates. em P /em -values less than 0.05 were considered statistically significant for all comparisons. Progression-free survival was defined as the interval from the time of enrolment to the date of first documented disease progression or patient’s death from any cause. Overall survival is considered the time interval from the date of enrolment until the date of death from any cause. The duration of response was measured from the first documentation of response to disease progression. Results Patients’ characteristics From June 2005 to June 2008, 336 patients with unresectable mCRC were enrolled into the study at 23 institutions throughout Greece. Two patients, in the CAPIRI+Bev Arm-B and one patient in the FOLFIRI+Bev Arm-A received no study treatment because they were found ineligible. The remained 333 were randomly allocated to receive front-line.
of patients /th th align=”center” valign=”top” charoff=”50″ rowspan=”1″ colspan=”1″ % /th th align=”center” valign=”top” charoff=”50″ rowspan=”1″ colspan=”1″ em P /em -value /th /thead Any12876122720