A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment
Snoeren N.,University Utrecht |
Voest E.E.,University Utrecht |
Bergman A.M.,Antonie Van Leeuwenhoek Hospital |
Dalesio O.,Antonie Van Leeuwenhoek Hospital |
And 5 more authors.
BMC Cancer | Year: 2010
Background: About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX.Methods/design: The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life.Conclusion: The HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA.Trial Registration: ClinicalTrials.gov Identifier NCT00394992. © 2010 Snoeren et al; licensee BioMed Central Ltd.
De Bruin C.D.E.,Albinusdreef |
Van Der Lugt N.M.,Albinusdreef |
Visser R.,Albinusdreef |
Van Zwet E.W.,Leiden University |
And 2 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2016
Objective: Small-for-gestational-age (SGA) neonates (birth weight <10th centile) are at higher risk of altered glucose homeostasis compared to appropriate for gestational age (AGA) neonates. The aim of this matched case-control study was to estimate the incidence of hypoglycaemia and/or hyperglycaemia in monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR).Methods: We included all MC twins with sIUGR (2002-2013). Neonates in the SGA group were matched with their AGA co-twin. We recorded the occurrence of hypoglycaemia and hyperglycaemia in the first 48 h after birth and studied the association with SGA.Results: In this retrospective study were 126 twin pairs included. The incidence of hypoglycaemia in the SGA group and AGA group was 29.6% and 17.4%, respectively, hyperglycaemia occurred in 8.7% of the SGA neonates and in 2.6% of the AGA co-twins. Multivariate analysis showed an independent association of SGA with hypoglycaemia (OR 1.97, CI 1.23-3.18, p ≤ 0.01), but not with hyperglycaemia (OR 2.57, CI 1.64-10.28, p = 0.182). Low gestational age (GA) at birth (OR 1.65, CI 1.09-2.48, p = 0.02) showed an independent association with hyperglycaemia.Conclusions: The risk of hypoglycaemia is almost twofold higher in SGA neonates compared to their MC AGA twins. Low GA appeared to be an independent risk factor for hyperglycaemia in SGA neonates. © 2015 Taylor & Francis.
Handgraaf H.J.M.,Albinusdreef |
Boogerd L.S.F.,Albinusdreef |
Verbeek F.P.R.,Albinusdreef |
Tummers Q.R.J.G.,Albinusdreef |
And 5 more authors.
Minimally Invasive Therapy and Allied Technologies | Year: 2016
Tumor involvement at the resection margin remains the most important predictor for local recurrence in patients with rectal cancer. A careful description of tumor localization is therefore essential. Currently, endoscopic tattooing with ink is customary, but visibility during laparoscopic resections is limited. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) could be an improvement. In addition to localize tumors, ICG can also be used to identify sentinel lymph nodes (SLNs). The feasibility of this new technique was explored in five patients undergoing laparoscopic low anterior resection for rectal cancer. Intraoperative tumor visualization was possible in four out of five patients. Fluorescence signal could be detected 32±18 minutes after incision, while ink could be detected 42 ± 21 minutes after incision (p = 0.53). No recurrence was diagnosed within three months after surgery. Ex vivo imaging identified a mean of 4.2 ± 2.7 fluorescent lymph nodes, which were appointed SLNs. One out of a total of 83 resected lymph nodes contained a micrometastasis. This node was not fluorescent. This technical note describes the feasibility of endoscopic tattooing of rectal cancer using ICG:nanocolloid and NIR fluorescence imaging during laparoscopic resection. Simultaneous SLN mapping was also feasible, but may be less reliable due to neoadjuvant therapy. © 2015 © Informa Healthcare.
Van Schinkel L.D.,Albinusdreef |
Willemse P.M.,Albinusdreef |
Van Der Meer R.W.,Leiden University |
Burggraaf J.,Center for Human Drug Research |
And 5 more authors.
British Journal of Cancer | Year: 2013
Background: After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC. Methods: Fourteen TC patients (age 34.6±12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated. Results: Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192±27 to 175±26 ml (P<0.05) and 109±18 to 95±16 ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87±0.43 to 1.64±0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39±0.05 to 0.36±0.05 (P<0.05). Conclusion: Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications. © 2013 Cancer Research UK. All rights reserved.