Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results
- PDF / 262,743 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 94 Downloads / 198 Views
PHASE II STUDIES
Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial Soledad Iseas 1 & Enrique L. Roca 1 & Juan M. O’Connor 2 & Martin Eleta 3 & Analia Sanchez-Luceros 4 & Daniela Di Leo 5 & Marcelo Tinelli 5 & Maria L. Fara 5 & Eduardo Spitzer 5 & Ignacio A. Demarco 6 & Giselle V. Ripoll 7 & Marina Pifano 7 & Juan Garona 7 & Daniel F. Alonso 7 Received: 7 January 2020 / Accepted: 14 February 2020 # The Author(s) 2020
Summary Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted. Clinical trial registration www.clinicaltrials.gov NCT01623206 Keywords Vasopressin peptide analog . Drug repurposing . Tumor perfusion . Hemostasis . von Willebrand factor . Gastrointestinal cancer Responsible Editor: Daniel F. Alonso * Daniel F. Alonso [email protected] 1
Oncology Unit, Gastroenterology Hospital Bonorino Udaondo, Buenos Aires, Argentina
2
Department of Clinical Oncology, Alexander Fleming Institute, Buenos Aires, Argentina
3
Onco-imaging Area, Imaxe Center for Diagnostic, Buenos Aires, Argentina
4
Thrombosis and Hemostasis Department, IMEX and IIHEMA, National Academy of Medicine, Buenos Aires, Argentina
5
Elea-Phoenix Laboratories, Los Polvorines, Argentina
6
Chemo-Romikin, Buenos Aires, Argentina
7
Laboratory of Molecular Oncology, National University of Quilmes, Bernal, Argentina
Introduction Colorectal cancer is one of the most common cancers worldwide, resulting in more than half a million deaths every year. While early-stage disease has a survival rate over
Data Loading...
