By Shreeya Nanda, Senior medwireNews Reporter
Phase III trial results support the use of intravenously administered PEGylated Escherichia coli asparaginase (PEG-asparaginase) as the preparation of choice in children and adolescents with acute lymphoblastic leukaemia (ALL).
The toxicity and efficacy profiles of PEG-asparaginase were comparable to those of the intramuscular native E. coli L-asparaginase preparation, but quality-of-life with respect to anxiety was significantly lower. Moreover, as a result of a longer half-life, PEG-asparaginase requires a less frequent dosing schedule, say the researchers, who recommend its use as “front-line treatment” for this patient population.
In the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05-001 (DFCI 05-001) trial, 463 of 551 newly diagnosed ALL patients aged 1–18 years achieved complete remission with 32 days of induction therapy. These patients were randomly allocated to receive either intravenous PEG-asparaginase (15 doses of 2500 IU/m2 every 2 weeks) or intramuscular native E. coli L-asparaginase (30 doses of 25,000 IU/m2 weekly).
The overall incidence of asparaginase-related side effects was comparable between the arms, at 28% for the 232 patients in the intravenous group and 26% for the 231 in the intramuscular group. Incidence rates of individual adverse events – such as allergy, pancreatitis and thrombotic or bleeding complications – also did not differ significantly.
Bacterial or fungal infections were the most frequent adverse event of grade 3 or higher in the intravenous PEG-asparaginase and the intramuscular native E. coli L-asparaginase groups, followed by asparaginase-related allergy. Two deaths, one in each treatment arm, were attributed to the study treatment.
After a median follow-up of 6 years, the 5-year disease-free and overall survival rates were also similar between patients given the intravenous and the intramuscular preparations, at 90% versus 89% and 96% versus 94%, respectively.
Both patients and parents or guardians reported significantly lower procedural and treatment anxiety, as assessed by the PedsQL questionnaire, with intravenous than with intramuscular asparaginase. But scores for pain and hurt, fatigue (either general or sleep/rest) were comparable, report Lewis Silverman (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and fellow DFCI 05-001 investigators.
The author of an accompanying commentary, published in The Lancet Oncology, say that the study “contributes to asparaginase treatment optimisation and monitoring”.
They add that these findings and those of other studies “reinforce the idea that intravenous PEG-asparaginase is the preparation that should be used in modern clinical trials commencing with the first planned exposure to the drug in the treatment schedule”, citing the reduction in the number of hospital visits, frequency of immunological reactions, and patient and parent anxiety.
Noting that ongoing trials have adopted the intravenous PEG-asparaginase, Carmelo Rizzari (University of Milano-Bicocca, Monza, Italy) concludes: “Hopefully soon, additional information will be available to enable us to finally choose not only the best asparaginase preparation but also the best schedule and treatment drug monitoring programme.”
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