Objective: It was the aim of this study to evaluate maintenance therapy with bevacizumab + capecitabine following induction with bevacizumab + capecitabine + oxaliplatin (XELOX) versus bevacizumab + XELOX until progression as first-line therapy in metastatic colorectal cancer (mCRC). Methods: Patients received either bevacizumab (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m² twice daily on days 1-14 + oxaliplatin 130 mg/m² on day 1 every 3 weeks) until disease progression (arm A) or the same doses of bevacizumab + XELOX for 6 cycles followed by bevacizumab + capecitabine until disease progression (arm B). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: One hundred and twenty-three patients were randomized. Treatment compliance was similar in both groups. Median PFS was significantly longer for arm B than for arm A (11.0 vs. 8.3 months; p = 0.002). There was no significant difference between the two arms for ORR (66.7 vs. 59.0%; p = 0.861) or median OS (23.8 vs. 20.2 months; p = 0.100). Tolerability was acceptable in both treatment arms; the most frequent grade 3/4 treatment-related adverse events (arm B vs. arm A) were fatigue (6.6 vs. 16.1%), diarrhoea (3.3 vs. 11.3%), anorexia (3.3 vs. 11.3%), and neuropathy (1.6 vs. 8.1%). Conclusions: Maintenance therapy with bevacizumab + capecitabine can be considered an appropriate option following induction bevacizumab + XELOX in patients with mCRC instead of continuation of bevacizumab + XELOX.

Abstract:The beneficial effects of estrogen on vasculature are partially explained by an estrogen-induced increase in nitric oxide (NO) synthesis. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase. In the present study, the effect of 17␤-estradiol (E2) on ADMA and NO synthesis was investigated both in vivo and in vitro. Plasma NO and ADMA levels were measured in healthy women at a low menstrual estrogenic stage (E2 Ͻ 100 pg/ml) and in women who were undergoing ovarian hyperstimulation (E2 Ͼ 2000 pg/ml) before in vitro fertilization embryo transfer. Primary human umbilical vein endothelial cell (HUVEC) cultures were incubated with and without 100 nM E2 for 24 hours and the NO and ADMA levels of the media were measured. A nitric oxide analyzer was used for the detection of NO metabolites. ADMA and L-arginine were measured by high-performance liquid chromatography after precolumn derivatization with o-phthaldialdehyde. The IVF patients with high plasma E2 concentrations had significantly lower (48%, n ϭ 12) plasma ADMA and higher (56%, n ϭ 14) NO levels than the women at a low estrogenic stage. The incubation of HUVEC cultures with estradiol resulted in a significant decrease (47%, n ϭ 10) in ADMA and an increase (46%, n ϭ 10) in NO concentration in the culture media. Estradiol, by reducing ADMA, may therefore facilitate NO synthesis in endothelial cells. The protective effects of estradiol on vasculature may partly be related to a reduction in ADMA levels.

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3565 Background: Colorectal cancer is one of the most frequent malignancies, second after breast cancer in women and third after lung cancer and prostate cancer in men. The aim of this study was to evaluate and compare the progression-free survival (PFS) between two arms: Arm A is a combination of BEV + XELOX; Arm B is a combination of BEV + XELOX for 6 cycles followed by maintenance BEV + capecitabine as first-line therapy in mCRC. Methods: BEV (7.5 mg/kg) + XELOX (capecitabine 1000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1 q3w) were administered until progression (Arm A) or 6 cycles of BEV + XELOX followed by BEV + capecitabine were administered until progression (Arm B). PFS was the primary endpoint; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. A sample size of 118 pts was required to detect with 80% power an increase of 1.5 months in median PFS between two arms with a standard deviation of 3.9 months and significance level of 0.05 (10% drop-out rate). Results: A total of 123 pts were randomized. Demographic characteristics were balanced between the arms. Median treatment period was 7.5 (range 0.5–13.9) and 8.1 (range 0.1–20.7) months in Arms A and B, respectively. There was a statistically significant difference in median PFS between arms, although there was no significant difference in ORR and OS (see table). Tolerability was acceptable in both arms with the following grade 3/4 adverse events (AEs): Arm A 48.4%; Arm B 34.4% (p=0.116). Grade 3/4 diarrhoea occurred in 9.7% vs. 3.3%, weakness in 8.1% vs. 8.2%, hand-foot syndrome in 3.2% vs. 1.6%, and neuropathy in 4.8% vs. 3.3% of pts in Arms A and B, respectively. Conclusions: These findings suggest that maintenance therapy with BEV + capecitabine following induction with 6 cycles of BEV + XELOX may be superior to continuous BEV + XELOX until progression inpts with previously untreated mCRC. [Table: see text]

299 Background: The contribution of metastasectomy to progression-free survival (PFS) and overall survival (OS) in patients (pts) with advanced stage colorectal cancer has been demonstrated in clinical trials. However, clinical trials may not represent the efficacy of treatment given to the whole population in daily practice, therefore evaluation of real-life data is needed. Methods: The demographic, pathological and clinical characteristics of 1064 RAS wild type pts were recorded in 28 centers in Turkey between January 2016 and March 2019 as part of the Onco-Colon Registry Program ( NCT04757311 ). Metastasectomy was performed in 169 patients (15.9%). In this study, pts with and without metastasectomy were compared in terms of demographic, histopathological and clinical features and treatment results. Results: Median follow-up time was 24 months(mos) (1-74), median age was 59 years (30-81). 32.5% of the pts were women. The proportion of pts with primary right colon was determined to be 16.8%. Synchronous metastasis was detected in 76.3% of those who underwent metastasectomy. Isolated liver metastasectomy was performed in 85.8% of the pts. It has been shown that 21.1% of the pts have MSI-H and 23.3% have a mucinous component. Metastasectomy was performed after conversion therapy in 54.8% of pts. In the patient group who underwent metastasectomy after medical treatment, the median time between the beginning of treatment and metastasectomy was found to be 7 mos (2-34). When the patient characteristics were compared, no significant difference was found between the groups with and without metastasectomy (p > 0.05). The median PFS (mPFS) was 13.5 mos in the group that underwent metastasectomy and 9.9 mos in the group that was not performed (p < 0.0001; HR: 0.63 (95% CI: 0.51-0.77). The median OS (mOS) was 47.3 mos in the group that underwent metastasectomy and 24.3 mos in the group without metastasectomy (p < 0.0001; HR: 0.36 (95% CI: 0.27-0.48). Conclusions: The significant contribution of metastasectomy on mPFS and mOS was shown in this reallife data based trial, where no difference was found in terms of general participation characteristics. In daily practice, prolonged mPFS and mOS emerges as pts who are followed-up radiologically at regular intervals from the beginning and who are appropriate for surgery have the chance of metastasectomy.