Asparagine Synthetase Expression and Phase I Study With L-Asparaginase Encapsulated in Red Blood Cells in Patients With Pancreatic Adenocarcinoma.

Abstract

OBJECTIVES:

Asparaginase encapsulated in erythrocytes (ERY-ASP) is a potentially effective drug in patients with pancreatic adenocarcinoma (PAC) with null/low asparagine synthetase (ASNS) expression. Our aims were to assess ASNS expression in PAC from a large cohort and its prognostic and/or predictive value and to conduct a phase I trial with ERY-ASP in patients with metastatic PAC.

METHODS:

Asparagine synthetase expression was evaluated using immunohistochemistry in resected PAC (471 patients) and in pairs of primary tumor and metastases (55 patients). Twelve patients were included in the phase I trial and received a single administration of ERY-ASP (25-150 IU/kg).

RESULTS:

Null/low ASNS expression was found in 79.4% of the resected PAC with a high concordance between primary tumor and metastases. Asparagine synthetase expression was significantly correlated with sex and CXCR4 expression. In the phase I trial, ERY-ASP was well tolerated by patients with metastatic PAC. No patient had DLTs, and 6 patients had at least 1 ERY-ASP causally related adverse event out of the 12 adverse events reported.

CONCLUSIONS:

Given the high rate of PAC with null/low ASNS expression and the good tolerability profile of ERY-ASP, ERY-ASP should be evaluated in further clinical studies in metastatic PAC.

• Authors: Jean-Baptiste Bachet, Fabien Gay, Raphaël Maréchal, Marie-Pierre Galais, Antoine Adenis, David Salako MsC, Jerome Cros, Pieter Demetter, Magali Svrcek, Armelle Bardier-Dupas, Jean-François Emile, Pascal Hammel, Christelle Ebenezer, Willy Berlier, Yann Godfrin, Thierry André
• Journal: Pancreas (Pancreas) Vol. 44 Issue 7 Pg. 1141-7 (Oct 2015) ISSN: 1536-4828 [Electronic] United States
• PMID: 26355551 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Asparaginase

Topics

• Adenocarcinoma (drug therapy, enzymology)
• Administration, Intravenous
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Asparaginase (adverse effects, biosynthesis, therapeutic use)
• Chemical and Drug Induced Liver Injury (etiology)
• Cohort Studies
• Drug Hypersensitivity (etiology)
• Erythrocyte Transfusion (adverse effects, methods)
• Erythrocytes (enzymology)
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Outcome Assessment, Health Care (methods, statistics & numerical data)
• Pancreatic Neoplasms (drug therapy, enzymology)
• Prognosis
• Proportional Hazards Models