Cargando…
A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients
Desmopressin (dDAVP) is a well-known peptide analog of the antidiuretic hormone vasopressin, used to prevent excessive bleeding during surgical procedures. dDAVP increases hemostatic mediators, such as the von Willebrand factor (vWF), recently considered a key element in resistance to metastasis. St...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540720/ https://www.ncbi.nlm.nih.gov/pubmed/26306290 http://dx.doi.org/10.1186/s40064-015-1217-y |
_version_ | 1782386278828867584 |
---|---|
author | Weinberg, Ruth S Grecco, Marcelo O Ferro, Gimena S Seigelshifer, Debora J Perroni, Nancy V Terrier, Francisco J Sánchez-Luceros, Analía Maronna, Esteban Sánchez-Marull, Ricardo Frahm, Isabel Guthmann, Marcelo D Di Leo, Daniela Spitzer, Eduardo Ciccia, Graciela N Garona, Juan Pifano, Marina Torbidoni, Ana V Gomez, Daniel E Ripoll, Giselle V Gomez, Roberto E Demarco, Ignacio A Alonso, Daniel F |
author_facet | Weinberg, Ruth S Grecco, Marcelo O Ferro, Gimena S Seigelshifer, Debora J Perroni, Nancy V Terrier, Francisco J Sánchez-Luceros, Analía Maronna, Esteban Sánchez-Marull, Ricardo Frahm, Isabel Guthmann, Marcelo D Di Leo, Daniela Spitzer, Eduardo Ciccia, Graciela N Garona, Juan Pifano, Marina Torbidoni, Ana V Gomez, Daniel E Ripoll, Giselle V Gomez, Roberto E Demarco, Ignacio A Alonso, Daniel F |
author_sort | Weinberg, Ruth S |
collection | PubMed |
description | Desmopressin (dDAVP) is a well-known peptide analog of the antidiuretic hormone vasopressin, used to prevent excessive bleeding during surgical procedures. dDAVP increases hemostatic mediators, such as the von Willebrand factor (vWF), recently considered a key element in resistance to metastasis. Studies in mouse models and veterinary trials in dogs with locally-advanced mammary tumors demonstrated that high doses of perioperative dDAVP inhibited lymph node and early blood-borne metastasis and significantly prolonged survival. We conducted a phase II dose-escalation trial in patients with breast cancer, administering a lyophilized formulation of dDAVP by intravenous infusion in saline, 30–60 min before and 24 h after surgical resection. Primary endpoints were safety and tolerability, as well as selection of the best dose for cancer surgery. Secondary endpoints included surgical bleeding, plasma levels of vWF, and circulating tumor cells (CTCs) as measured by quantitative PCR of cytokeratin-19 transcripts. Only 2 of a total of 20 patients experienced reversible adverse events, including hyponatremia (grade 4) and hypersensitivity reaction (grade 2). Reactions were adequately managed by slowing the infusion rate. A reduced intraoperative bleeding was noted with increasing doses of dDAVP. Treatment was associated with higher vWF plasma levels and a postoperative drop in CTC counts. At the highest dose level evaluated (2 μg/kg) dDAVP appeared safe when administered in two slow infusions of 1 μg/kg, before and after surgery. Clinical trials to establish the effectiveness of adjunctive perioperative dDAVP therapy are warranted. This trial is registered on www.clinicaltrials.gov (NCT01606072). |
format | Online Article Text |
id | pubmed-4540720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-45407202015-08-24 A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients Weinberg, Ruth S Grecco, Marcelo O Ferro, Gimena S Seigelshifer, Debora J Perroni, Nancy V Terrier, Francisco J Sánchez-Luceros, Analía Maronna, Esteban Sánchez-Marull, Ricardo Frahm, Isabel Guthmann, Marcelo D Di Leo, Daniela Spitzer, Eduardo Ciccia, Graciela N Garona, Juan Pifano, Marina Torbidoni, Ana V Gomez, Daniel E Ripoll, Giselle V Gomez, Roberto E Demarco, Ignacio A Alonso, Daniel F Springerplus Research Desmopressin (dDAVP) is a well-known peptide analog of the antidiuretic hormone vasopressin, used to prevent excessive bleeding during surgical procedures. dDAVP increases hemostatic mediators, such as the von Willebrand factor (vWF), recently considered a key element in resistance to metastasis. Studies in mouse models and veterinary trials in dogs with locally-advanced mammary tumors demonstrated that high doses of perioperative dDAVP inhibited lymph node and early blood-borne metastasis and significantly prolonged survival. We conducted a phase II dose-escalation trial in patients with breast cancer, administering a lyophilized formulation of dDAVP by intravenous infusion in saline, 30–60 min before and 24 h after surgical resection. Primary endpoints were safety and tolerability, as well as selection of the best dose for cancer surgery. Secondary endpoints included surgical bleeding, plasma levels of vWF, and circulating tumor cells (CTCs) as measured by quantitative PCR of cytokeratin-19 transcripts. Only 2 of a total of 20 patients experienced reversible adverse events, including hyponatremia (grade 4) and hypersensitivity reaction (grade 2). Reactions were adequately managed by slowing the infusion rate. A reduced intraoperative bleeding was noted with increasing doses of dDAVP. Treatment was associated with higher vWF plasma levels and a postoperative drop in CTC counts. At the highest dose level evaluated (2 μg/kg) dDAVP appeared safe when administered in two slow infusions of 1 μg/kg, before and after surgery. Clinical trials to establish the effectiveness of adjunctive perioperative dDAVP therapy are warranted. This trial is registered on www.clinicaltrials.gov (NCT01606072). Springer International Publishing 2015-08-19 /pmc/articles/PMC4540720/ /pubmed/26306290 http://dx.doi.org/10.1186/s40064-015-1217-y Text en © Weinberg et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Weinberg, Ruth S Grecco, Marcelo O Ferro, Gimena S Seigelshifer, Debora J Perroni, Nancy V Terrier, Francisco J Sánchez-Luceros, Analía Maronna, Esteban Sánchez-Marull, Ricardo Frahm, Isabel Guthmann, Marcelo D Di Leo, Daniela Spitzer, Eduardo Ciccia, Graciela N Garona, Juan Pifano, Marina Torbidoni, Ana V Gomez, Daniel E Ripoll, Giselle V Gomez, Roberto E Demarco, Ignacio A Alonso, Daniel F A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
title | A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
title_full | A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
title_fullStr | A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
title_full_unstemmed | A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
title_short | A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
title_sort | phase ii dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540720/ https://www.ncbi.nlm.nih.gov/pubmed/26306290 http://dx.doi.org/10.1186/s40064-015-1217-y |
work_keys_str_mv | AT weinbergruths aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT greccomarceloo aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT ferrogimenas aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT seigelshiferdeboraj aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT perroninancyv aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT terrierfranciscoj aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT sanchezlucerosanalia aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT maronnaesteban aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT sanchezmarullricardo aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT frahmisabel aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT guthmannmarcelod aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT dileodaniela aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT spitzereduardo aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT cicciagracielan aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT garonajuan aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT pifanomarina aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT torbidonianav aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT gomezdaniele aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT ripollgisellev aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT gomezrobertoe aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT demarcoignacioa aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT alonsodanielf aphaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT weinbergruths phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT greccomarceloo phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT ferrogimenas phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT seigelshiferdeboraj phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT perroninancyv phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT terrierfranciscoj phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT sanchezlucerosanalia phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT maronnaesteban phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT sanchezmarullricardo phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT frahmisabel phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT guthmannmarcelod phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT dileodaniela phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT spitzereduardo phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT cicciagracielan phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT garonajuan phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT pifanomarina phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT torbidonianav phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT gomezdaniele phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT ripollgisellev phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT gomezrobertoe phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT demarcoignacioa phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients AT alonsodanielf phaseiidoseescalationtrialofperioperativedesmopressin1desamino8dargininevasopressininbreastcancerpatients |