35 research outputs found
ACE Inhibition and Endothelial Function: Main Findings of PERFECT, a Sub-Study of the EUROPA Trial
Background: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction.
Methods: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months.
Results: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval −0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07).
Conclusion: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD
ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy
This work was supported by KWF Dutch Cancer Society (UVA 2012–5607 and UVA 2013–5932
Cachexia, dietetic consultation, and survival in patients with pancreatic and periampullary cancer: A multicenter cohort study
It is unclear to what extent patients with pancreatic cancer have cachexia and had a
dietetic consult for nutritional support. The aim was to assess the prevalence of cachexia, dietitian consultation, and overall survival in these patients. This prospective
multicenter cohort study included patients with pancreatic cancer, who participated in
the Dutch Pancreatic Cancer Project and completed patient reported outcome measures
(2015–2018). Additional data were obtained from the Netherlands Cancer Registry.
Cachexia was defined as self-reported >5% body weight loss, or >2% in patients with a
BMI <20 kg/m2
over the past half year. The Kaplan–Meier method was used to analyze
overall survival. In total, 202 patients were included from 18 centers. Cachexia was
present in 144 patients (71%) and 81 of those patients (56%) had dietetic consultation.
Cachexia was present in 63% of 94 patients who underwent surgery, 77% of 70 patients who received palliative chemotherapy and 82% of 38 patients who had best supportive
care. Dietitian consultation was reported in 53%, 52%, and 71%, respectively. Median
overall survival did not differ between patients with and without cachexia, but decreased
in those with severe weight loss (12 months (IQR 7–20) vs. 16 months (IQR 8–31),
p = 0.02), as compared to those with <10% weight loss during the past half year. Twothirds of patients with pancreatic cancer present with cachexia of which nearly half had
no dietetic consultation. Survival was comparable in patients with and without cachexia,
but decreased in patients with more severe weight loss
1685TiP Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3):A multicenter randomized controlled trial
BackgroundSurgical resection followed by adjuvant mFOLFIRINOX is the current standard of care for patients with resectable pancreatic cancer. The main concern with adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.Trial designThis is a multicentre, phase III, RCT that will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centres and three centres in Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 hours continuous infusion of 5-fluorouracil 2400 g/m2) followed by surgery and 4 cycles of adjuvant mFOLFIRINOX. Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Accrual started on September 7, 2021, and as of May 10, 2023, all centres are open for inclusion and 138 patients have been randomized
1685TiP Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3):A multicenter randomized controlled trial
BackgroundSurgical resection followed by adjuvant mFOLFIRINOX is the current standard of care for patients with resectable pancreatic cancer. The main concern with adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.Trial designThis is a multicentre, phase III, RCT that will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centres and three centres in Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 hours continuous infusion of 5-fluorouracil 2400 g/m2) followed by surgery and 4 cycles of adjuvant mFOLFIRINOX. Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Accrual started on September 7, 2021, and as of May 10, 2023, all centres are open for inclusion and 138 patients have been randomized