Frequency of target attainment and toxicity with reduced PEG-asparaginase (PEG) dosing in acute lymphoblastic leukemia (ALL)
| العنوان: | Frequency of target attainment and toxicity with reduced PEG-asparaginase (PEG) dosing in acute lymphoblastic leukemia (ALL) |
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| المؤلفون: | Trevor N Christ, Mitchell Streck, Randall W. Knoebel, Wendy Stock |
| المصدر: | Journal of Clinical Oncology. 35:e18501-e18501 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Cancer Research, Asparaginase, PEG-asparaginase, business.industry, Lymphoblastic Leukemia, Incidence (epidemiology), macromolecular substances, Pharmacology, chemistry.chemical_compound, Oncology, chemistry, Toxicity, PEG ratio, Target attainment, Medicine, Dosing, business |
| الوصف: | e18501 Background: Asparaginase (ASN) is a critical part of ALL therapy; however, in adults, a higher incidence of toxicities results in treatment delays and suboptimal exposure. We have reported a higher rate of PEG toxicity in pts > 50 yrs of age, baseline liver dysfunction, diabetes, and obesity (BMI ≥ 30). Thus, we hypothesized that reducing the PEG dose from 2500 units/m2 to 1000 units/m2 with further reduction to 500 units/m2 if any of those co-morbidities were present would reduce toxicities and still achieve therapeutic ASN levels. Methods: This is a single-center, retrospective study that included adult pts with ALL. Pts must have received at least one dose of PEG using a pediatric inspired regimen that includes 7 doses of PEG. The primary objective was to determine the rate of target ASN activity (≥ 0.1 IU/mL) one week after administration of reduced PEG during induction. Secondary objectives included the incidence of grade 3/4 toxicity based upon CTACE 4 criteria (hepatotoxicity, pancreatitis, hypertriglyceridemia, and VTE) between standard (SD) > 1000 units/m2 and reduced (RED) ≤1000 units/m2 PEG dosing. Results: 41 consecutive pts with ALL were included. Median age was 43 years (range 18-76). Median WBC upon admission was 7.6. At baseline, 25 pts (61%) had at least one comorbidity. 26 pts (63%) received SD PEG and 15 pts (37%) received RED PEG with median dose 1000 units/m2. 80% of pts achieved target ASN activity following administration of a RED PEG induction dose, median level of 0.1 IU/mL (IQR 0.1-0.24 IU/mL). 30 pts (73%) experienced grade 3/4 toxicity during induction, 81% in the SD group vs 60% in the RED group (p = 0.3). During induction, grade 3/4 hepatotoxicity was seen in 16 SD pts (62%) vs 6 RED pts (40%) (p = 0.211). Grade 3/4 hyperbilirubinemia was seen in 12 SD pts (46%) vs 1 RED pt (7%) (p = 0.014). Conclusions: The majority of pts attained a therapeutic ASN activity level with RED PEG. This resulted in a trend towards lower incidence of overall toxicity and a significant decrease in hyperbilirubinemia. A larger prospective study will be needed to determine whether decreased toxicity during induction correlates with fewer treatment delays, improved drug delivery, and better treatment outcome. |
| تدمد: | 1527-7755 0732-183X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3fa71d4638ca44f49d3f445e70b11fdd https://doi.org/10.1200/jco.2017.35.15_suppl.e18501 |
| رقم الأكسشن: | edsair.doi...........3fa71d4638ca44f49d3f445e70b11fdd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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