L-Asparaginase

Question 1

What’s the function of L-asparagine?

Answer 1

• it’s an non-essential amino acid
• involved in cell functioning, nerve, and brain function
• requires the enzyme, Asparaginase, which is constitutive in many tissues, but not lymphoblasts

Question 2

What are some mechanisms of resistance of Elspar?

Answer 2

resistance happen rapidly when used as single agent
- drug exposure –> upregulation of asparagine synthase
- development of neutralizing antibodies –> silent hypersensitivity

Question 3

What are some side effects of Elspar?

Answer 3

• hypersensitivity: seen in up to 40% of patients, but <20% in combination therapy
• signs of hypersensitivity = urticaria, hypotension
• pancreatitis
• decreased clotting factors: vitamin K dependent, anti-thrombin III
• Hyperammonemia

Question 4

What are some drugs interactions with Elspar?

Answer 4

• can terminate action of methotrexate –> inhibition of polygoutamination –> less tumour cell retention
• the decrease in circulating albumin levels –> less protein binding –> increase clearance

Question 5

What happens if there is a depletion of L-asparagine?

Answer 5

inhibition of protein synthesis

Question 6

How common is hyperammonemia after Elspar in dogs?

Answer 6

seen in about 19%, but clinical cases are very infrequent
- neurological, vomiting, sever events = rare

Question 7

How does Elspar change cPLI?

Answer 7

no clinical pancreatitis noted based on cPLI and clinical signs, though subclinical pancreatitis could be present
(GI signs may be due to chemo side effects rathe than pancreatitis)

Question 8

How common is hypersensitivity after Elspar?

Answer 8

<5% (in 142 dogs and 68 cats)
- more rare in cats

Question 9

How do cats with LSA respond to Elspar?

Answer 9

30% ORR - 2 CR, 2 PR, 4 SD, 5 PD
Maybe the multicentric (2 complete 1 partial) and gastric form (1 partial) are more sensitive