Introduction

L-asparaginase is a frequently used drug in L-CHOP protocols in the treatment of canine malignant lymphoma. Since production and availability of native E. coli-derived L-asparaginase is limited in various European countries, PEG-L-asparaginase (PEG-ASP) is a commonly used alternative. The objective of this study is to find the minimal dosage and dose interval of PEG-ASP in dogs.

Materials and Methods

Multi-phase clinical dose finding study with seven healthy Beagle dogs. Plasma amino acid concentrations (including asparagine and aspartic acid) and PEG-ASP were measured at various time points after subcutaneous administration of different dosages PEG-ASP.

Results

Administration of 10 IU/kg PEG-ASP resulted in asparagine suppression in all dogs for various durations; 9 days in all seven dogs, 15 days in five dogs, 21 days in three dogs and 29 days in one dog. Subsequent administration of a second dose of 20 IU/kg PEG-ASP resulted in asparagine suppression shorter than 9 days in five dogs. Plasma asparagine suppression was seen at PEG-ASP plasma concentrations of 22 IU/L.

Conclusions

There appears to be great individual variation in response to PEG-ASP. A dose of 10 IU/kg PEG-ASP was already sufficient in all dogs for a minimal asparagine suppression of 9 days, although a great variation existed in the maximal period of suppression. Previously thought to be less immunogenic than L-asparaginase, resistance to PEG-ASP seems to appear frequently and can occur after one injection. Although PEG-ASP plasma concentrations of 100 IU/L are considered the minimal therapeutic level in humans, asparagine suppression occurs already with PEG-ASP plasma concentrations of less than 25 IU/L in the canine samples.