Publications by authors named "Kristina Middelberg-Bisping"

2 Publications

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Nutrition and gastroenterological support in end of life care.

Best Pract Res Clin Gastroenterol 2020 Oct - Dec;48-49:101692. Epub 2020 Oct 14.

Department of Medicine II, University Hospital, LMU Munich, Marchioninistraße 15, Munich, 81377, Germany.

Malnutrition and the broad spectrum of cancer cachexia frequently occur in patients with malignant disease of all tumour stages and impact on survival and quality of life of patients. Structured screening for the risk of malnutrition with validated tools and nutritional assessment are the prerequisite for adequate nutritional support in cancer patients. In patients receiving tumour directed therapy, the patients diet should meet the requirements to give optimal support, while later on comfort feeding is part of symptom focused palliation. The basis of nutritional support in a malnourished patient is nutritional counselling, and nutritional support can be offered within a step-up approach meeting the patient's needs. A combination of nutritional support with interventions targeting metabolic changes and physical exercise is suggested to treat cancer cachexia.
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January 2021

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study.

Cancers (Basel) 2020 Jun 7;12(6). Epub 2020 Jun 7.

Department of Medicine A, Hematology, Oncology, University Hospital Muenster, D-48149 Muenster, Germany.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction.

Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts.

Results: MTD was 3 mg/m tTF-NGR/day × 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t of 8 to 9 h without accumulation in daily administrations.

Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.
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June 2020