1 INTRODUCTION
Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children as it represents approximately 25% of cancer diagnoses among children below 15 years. Management of ALL has evolved over many decades; with a risk-based approach, treatment intensification, and better supportive care, survival rates in children have progressively risen to nearly 90%.1 L‑Asparaginase is an integral component of treatment for children with ALL and since its introduction by the Dana Farber group in 1977 into pediatric treatment protocols survival has significantly improved.2,3
There are three currently available L-Asparaginase preparations approved for clinical applications: Escherichia coli derived native E.coli Asparaginase, PEGylated Asparaginase (PEG Asparaginase), and Erwinia chrysanthemi derived Erwinia Asparaginase. All presently available Asparaginase preparations share the same mechanism of action – the deamination and depletion of asparagine, an essential amino acid for the lymphoblast. Yet, each displays a markedly different pharmacokinetic profile.4,5. PEG Asparaginase has a significantly longer half-life and is less immunogenic than the native Asparaginase.6 When used in front-line therapy to replace native Asparaginase as part of combination chemotherapy, PEG Asparaginase has shown comparable efficacy.7
In clinical practice, the enzyme is currently given by the intravenous, intramuscular or subcutaneous route, with dosages being different across various protocols followed.8 Asparaginase activity of 100 IU/L at desired time point for the molecule is considered to be sufficient for complete asparagine depletion.9Although this might theoretically result in different pharmacokinetic profiles, information on the comparability of the routes of administration is limited about the currently available preparations.
Therapeutic drug monitoring of Serum Asparaginase Activity (SAA) level helps individualise Asparaginase dosing. The common side effects encountered with Asparaginase are hypersensitivity reactions, silent inactivation, cerebral sinus venous thrombosis, pancreatitis, hyperglycemia, hypertriglyceridemia, and liver dysfunction (hyperbilirubinemia and transaminitis). There is heterogeneity among healthcare providers in the usage of L-Asparaginase concerning preparations used, doses and route of administration, therapeutic drug monitoring, and toxicity profile observed along with dilemma of choosing a bioequivalent drug. The present survey attempts to understand the Asparaginase usage practice among healthcare providers in India, which will pave the way for effective designing of future clinical trials associated with pediatric oncology.