Morning and afternoon appetite and gut hormone responses to meal and stress challenges in obese individuals with and without binge eating disorder.

BACKGROUND: Eating late in the day is common, and stress can induce eating. Little is understood about how time of day and stress interact to affect appetite and thereby body weight. These may be particularly important influences in binge eaters, who tend to binge in the evening, and in response to stress. METHOD: Obese participants with (n=16) and without (n=16) binge eating disorder (BED) participated in two identical test protocols beginning either in the morning or the afternoon (AM condition/PM condition), each following an 8 h fast. For each protocol, they first received a standardized liquid meal (0900/1600 hours), then a stress test (Socially Evaluated Cold Pressor Test, 1110/1810 hours), and then a multi-item ad libitum buffet meal (1140/1840 hours) while rating appetite and stress and having blood drawn for hormone measures. RESULTS: Appetite at baseline was greater in the PM than in the AM condition (higher hunger, lower fullness). Following the liquid meal, area under the curve (AUC) values for hunger and ghrelin were greater and AUC values for peptide YY lower in the PM than in the AM condition. Only those with BED showed lower fullness AUC in the PM condition, as well as a pattern of higher initial PM and lower initial AM ghrelin. Following the stress test, cortisol and ghrelin increased in both the AM and PM conditions, but higher ghrelin AUC and lower cortisol AUC were observed in the PM condition. Again, only participants with BED showed lower fullness AUC in the PM condition. Buffet meal intake was similar across groups and conditions but those with BED reported greater loss of control and binge resemblance than those without. CONCLUSIONS: Afternoon/evening may be a high-risk period for overeating, particularly when paired with stress exposure, and for those with binge eating.

Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: final results from a randomised phase II study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan (FNCLCC ACCORD 13/0503 study).

BACKGROUND: The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC. PATIENTS AND METHODS: Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate. RESULTS: A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively). CONCLUSIONS: This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.

A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer.

BACKGROUND: To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer. PATIENTS AND METHODS: In this randomized phase II trial, 80 patients were treated: arm A (IRINOX) in 40 patients received at day 1 oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) biweekly, standard arm B received a biweekly simplified folinic acid (FA) and fluorouracil (FU), FA 200 mg/m(2) in a 2-h infusion and bolus injection of 5FU 400 mg/m(2) on day 1, then a two 400 mg/m(2) continuous infusion of FU on days 1 and 2 with either oxaliplatin 85 mg/m(2) (20 patients) or irinotecan 180 mg/m(2) (20 patients). RESULTS: Twenty-one partial responses (52.5%, median duration 7.2 months) were observed with the IRINOX arm and two complete and 20 partial responses (55%, median duration 6.4 months) with arm B. Median progression-free and overall survival times were 8.4 and 19 months, respectively, in the IRINOX arm and 8.1 and 20.4 months in arm B. Main grade 3/4 toxic effects were, respectively, neutropenia 42.5% and 32.5%; febrile neutropenia 10% and 5%; diarrhea 32.5% and 7.5%; vomiting 10.0% and 5%; neurosensory toxicity 17.5% and 7.5%. CONCLUSION: The IRINOX arm has a manageable toxicity and is active.