title: A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients.
abstract: 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).
authors: Gynecology Service, Anesthesiology Service, Allergy and Immunology Unit and Central Laboratory, 'Eva Peron' Hospital, San Martín, Argentina.
authors: Ruth S
authors: RS
authors: Weinberg
authors: Gynecology Service, Anesthesiology Service, Allergy and Immunology Unit and Central Laboratory, 'Eva Peron' Hospital, San Martín, Argentina.
authors: Marcelo O
authors: MO
authors: Grecco
authors: Gynecology Service, Anesthesiology Service, Allergy and Immunology Unit and Central Laboratory, 'Eva Peron' Hospital, San Martín, Argentina.
authors: Gimena S
authors: GS
authors: Ferro
authors: Gynecology Service, Anesthesiology Service, Allergy and Immunology Unit and Central Laboratory, 'Eva Peron' Hospital, San Martín, Argentina.
authors: Debora J
authors: DJ
authors: Seigelshifer
authors: Gynecology Service, Anesthesiology Service, Allergy and Immunology Unit and Central Laboratory, 'Eva Peron' Hospital, San Martín, Argentina.
authors: Nancy V
authors: NV
authors: Perroni
authors: Breast Pathology Unit, Italian Hospital, La Plata, Argentina.
authors: Francisco J
authors: FJ
authors: Terrier
authors: Thrombosis and Hemostasis Department, National Academy of Medicine, IMEX-ANM, Buenos Aires, Argentina.
authors: Analía
authors: A
authors: Sánchez-Luceros
authors: Pathology Service, Mater Dei Sanatorium, Buenos Aires, Argentina.
authors: Esteban
authors: E
authors: Maronna
authors: Pathology Service, Mater Dei Sanatorium, Buenos Aires, Argentina.
authors: Ricardo
authors: R
authors: Sánchez-Marull
authors: Pathology Service, Mater Dei Sanatorium, Buenos Aires, Argentina.
authors: Isabel
authors: I
authors: Frahm
authors: Elea Laboratories, Buenos Aires, Argentina.
authors: Marcelo D
authors: MD
authors: Guthmann
authors: Elea Laboratories, Buenos Aires, Argentina.
authors: Daniela
authors: D
authors: Di Leo
authors: Elea Laboratories, Buenos Aires, Argentina.
authors: Eduardo
authors: E
authors: Spitzer
authors: Chemo-Romikin, Buenos Aires, Argentina.
authors: Graciela N
authors: GN
authors: Ciccia
authors: Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. Sáenz Peña 352, Bernal, B1876BXD Buenos Aires, Argentina.
authors: Juan
authors: J
authors: Garona
authors: Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. Sáenz Peña 352, Bernal, B1876BXD Buenos Aires, Argentina.
authors: Marina
authors: M
authors: Pifano
authors: Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. Sáenz Peña 352, Bernal, B1876BXD Buenos Aires, Argentina.
authors: Ana V
authors: AV
authors: Torbidoni
authors: Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. Sáenz Peña 352, Bernal, B1876BXD Buenos Aires, Argentina.
authors: Daniel E
authors: DE
authors: Gomez
authors: Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. Sáenz Peña 352, Bernal, B1876BXD Buenos Aires, Argentina.
authors: Giselle V
authors: GV
authors: Ripoll
authors: Elea Laboratories, Buenos Aires, Argentina.
authors: Roberto E
authors: RE
authors: Gomez
authors: Chemo-Romikin, Buenos Aires, Argentina.
authors: Ignacio A
authors: IA
authors: Demarco
authors: Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. Sáenz Peña 352, Bernal, B1876BXD Buenos Aires, Argentina.
authors: Daniel F
authors: DF
authors: Alonso
keywords: Breast cancer trial; Circulating tumor cells; Hemostasia; Surgery; dDAVP; von Willebrand factor