J Pain Palliative Care Pharmacother 2011; 25: 340–9.CrossRef”
“Introduction L-asparaginase (ASNase) is an important oncotherapy, particularly for acute lymphoblastic leukemia LGX818 nmr (ALL). Tucidinostat cell line ASNase is thought to exert its anti-tumor activity by hydrolyzing asparagine to aspartate and ammonia. Asparagine synthetase activity

in some malignant lymphoblasts is very low, and the lymphoblasts rely on an exogenous supply of amino acids. Lymphoblasts thereby deplete the supply of asparagine, which leads to cell death.[1–3] An advantage of ASNase is that it does not have cross-resistance with other anti-tumor agents. Another important advantage is that it has low toxicity in normal tissues and VS-4718 in other neoplastic cells that express high levels of asparagine synthetase. Potential side effects of ASNase include hypersensitivity reactions, central nervous system dysfunction, coagulation abnormalities, liver dysfunction, hyperglycemia, hyperlipemia, and pancreatitis.[4] In some cases,

ASNase-induced pancreatitis can be life threatening and all chemotherapy must be discontinued. Although patients can recover from this kind of acute pancreatitis, re-initiation of therapy with ASNase in such cases is generally considered contraindicated. There are various treatments for ASNase-induced pancreatitis: some reports have suggested mafosfamide use of octreotide[5–7] or a continuous regional arterial infusion of a protease inhibitor

and antibiotics.[8] Although pancreatitis remains one of the most severe complications of ASNase therapy, it is impossible to predict who will develop pancreatic toxicity from ASNase.[9] Furthermore, there is no adequate prophylaxis for this potentially life-threatening condition. In the present study, the pharmacologic effects of ASNase on plasma amino acid levels and serum rapid turnover protein (RTP) levels were investigated as factors potentially related to ASNase-induced pancreatic injury. The presence of pancreatitis or pancreatic injury during administration of ASNase was evaluated through measurement of the levels of serum pancreatic enzymes and pancreatic protease inhibitors. Methods Subjects The study group consisted of 29 children aged 1 year to 13.25 years (median age 4 years; male : female ratio 19 : 10) who were newly diagnosed with ALL and received chemotherapy for ALL (B-cell phenotype : T-cell phenotype ratio 25 : 4). Patients were classified as standard risk (SR) if they met the following criteria: age 1–9.99 years and white blood cell count <50 000/μL. All others were designated as high risk (HR) [SR : HR ratio 18 : 11]. Induction therapy was initiated according to the Tokyo Children’s Cancer Study Group L04-16 protocol and consisted of prednisolone 60 mg/m2/day (on days 1–35, tapering off on days 36–42); vincristine 1.