Children with acute lymphoblastic leukemia (ALL), the most common form of pediatric cancer, can safely receive intravenous infusions of a reformulated mainstay of chemotherapy that has been delivered via painful intramuscular injection for more than 40 years, research suggests.
Researchers looked at the four-year, event-free survival and toxicity of E. coli L-asparaginase delivered via IV in its polyethylene glycol (PEG)-conjugated formulation or through IM injection in its native formulation. Clinicians had been delivering the drug via injection because of serious allergic reactions previously linked with IV infusion of the drug in its native form.
The clinical trial is one of the largest to compare the safety, efficacy and pharmokinetics of the two formulations of the bacteria-based enzyme. Findings from the study, DFCI ALL Consortium Protocol 05-001, were presented at the 55th annual meeting of the American Society of Hematology. Data came from 551 patients, 1 to18 years old, who were treated for pediatric ALL at 11 centers in the United States and Canada between 2005 and 2010. The findings take on particular relevance now that native L-asparaginase is no longer available in the U.S.
"Demonstrating that this important agent can be safely administered intravenously should help to provide clinicians peace of mind that they can decrease patient discomfort without increasing risk," said Lewis B. Silverman, MD, director of the Hematologic Malignancy Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, who presented the data on behalf of the Dana-Farber Cancer Institute ALL Consortium.
The overall four-year event-free survival rate for all patients enrolled on the protocol was 86 percent, among the highest rates ever reported in a pediatric ALL trial. There was no statistically significant difference in event-free survival between patients in the trial's IV PEG-asparaginase and IM native L-asparaginase arms (92 and 90 percent, respectively). Nor were there significant differences in the rates of allergic reactions (12 and 9 percent, respectively), pancreatitis (11 and 9 percent, respectively) or clotting (6 and 11 percent, respectively), all of which are potential side effects of L-asparaginase.
PEG-asparaginase remains in the blood stream longer than L-asparaginase, which means patients can be treated less frequently. Researchers found that the lowest concentrations of drug in the blood of patients in the study's IV PEG-asparaginase arm were nearly eight times higher than those in the IM native E. coli L-asparaginase group.
Through patient and parent surveys, the study also demonstrated that pediatric patients experienced less pain and anxiety with IV administration of PEG-asparaginase.
PEG-asparaginase is a modified formulation of E. coli-derived L-asparaginase. Previous studies had indicated that PEG-asparaginase may be less allergenic, suggesting that IV administration of the drug might be more feasible than the native E. coli preparation. However, when Protocol 05-001 opened, most oncologists were continuing to administer PEG-asparaginase as an IM injection. At that time, no large trial had directly compared the efficacy of the IV versus IM administration of asparaginase.
Protocol 05-001 also investigated an intensified treatment regimen for children with B cell ALL who showed evidence of high levels of minimal residual disease following initial treatment, who tend to have relatively poor outcomes. The intensified regimen was associated with a four-year event-free survival rate of 77 percent, a large improvement over outcomes reported in the past for this group of patients.
The study was supported by the National Cancer Institute (grant number P01CA068484) and in part by Enzon Pharmaceuticals, which made PEG-asparaginase (Oncaspar) at the time of the trial. Silverman and several co-authors have served on advisory boards for Signma Tau Pharmaceuticals, which currently manufactures Oncaspar.
The Dana-Farber/Boston Children's Cancer and Blood Disorders Center brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since 1947. The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children's Hospital and outpatient care at the Dana-Farber Cancer Institute's Jimmy Fund Clinic. Dana-Farber/Boston Children's brings the results of its pioneering research and clinical trials to patients' bedsides through five clinical centers: the Blood Disorders Center, the Brain Tumor Center, the Hematologic Malignancies Center, the Solid Tumors Center, and the Stem Cell Transplant Center.
Irene Sege | EurekAlert!
Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy