Schliemann, Christoph; Gerwing, Mirjam; Heinzow, Hauke; Harrach, Saliha; Schwoeppe, Christian; Wildgruber, Moritz; Hansmeier, Anna A.; Angenendt, Linus; Berdel, Andrew F.; Stalmann, Ursula; Berning, Björna; Kratz-Albers, Karsten; Middelberg-Bisping, Kristina; Wiebe, Stefanie; Albring, Joern; Wilms, Christian; Hartmann, Wolfgang; Wardelmann, Eva; Kraehling, Tobias; Heindel, Walter; Gerss, Joachim; Bormann, Eike; Schmidt, Hartmut; Lenz, Georg; Kessler, Torsten; Mesters, Rolf M.; Berdel, Wolfgang E. (2020): 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. In: Cancers, Vol. 12, No. 6, 1488 |
Abstract
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(2)tTF-NGR/day x 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(1/2(terminal))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.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
Language: | English |
ID Code: | 87538 |
Deposited On: | 25. Jan 2022 09:24 |
Last Modified: | 25. Jan 2022 09:24 |
- BASE
- Schliemann, Christoph
- Gerwing, Mirjam
- Heinzow, Hauke
- Harrach, Saliha
- Schwoeppe, Christian
- Wildgruber, Moritz
- Hansmeier, Anna A.
- Angenendt, Linus
- Berdel, Andrew F.
- Stalmann, Ursula
- Berning, Björna
- Kratz-Albers, Karsten
- Middelberg-Bisping, Kristina
- Wiebe, Stefanie
- Albring, Joern
- Wilms, Christian
- Hartmann, Wolfgang
- Wardelmann, Eva
- Kraehling, Tobias
- Heindel, Walter
- Gerss, Joachim
- Bormann, Eike
- Schmidt, Hartmut
- Lenz, Georg
- Kessler, Torsten
- Mesters, Rolf M.
- Berdel, Wolfgang E.
- Google Scholar
- Schliemann, Christoph
- Gerwing, Mirjam
- Heinzow, Hauke
- Harrach, Saliha
- Schwoeppe, Christian
- Wildgruber, Moritz
- Hansmeier, Anna A.
- Angenendt, Linus
- Berdel, Andrew F.
- Stalmann, Ursula
- Berning, Björna
- Kratz-Albers, Karsten
- Middelberg-Bisping, Kristina
- Wiebe, Stefanie
- Albring, Joern
- Wilms, Christian
- Hartmann, Wolfgang
- Wardelmann, Eva
- Kraehling, Tobias
- Heindel, Walter
- Gerss, Joachim
- Bormann, Eike
- Schmidt, Hartmut
- Lenz, Georg
- Kessler, Torsten
- Mesters, Rolf M.
- Berdel, Wolfgang E.