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Journal of Oncology Pharmacy Practice :... Jun 2024Rapidly increasing costs of medication acquisition can pose a challenge for health-system pharmacy budgets. The impact of dose-rounding in a pediatric oncology...
INTRODUCTION
Rapidly increasing costs of medication acquisition can pose a challenge for health-system pharmacy budgets. The impact of dose-rounding in a pediatric oncology population has not previously been well documented and a retrospective review was undertaken to quantify the potential cost benefits.
METHODS
A retrospective chart review of patients with an oncologic diagnosis was performed for cytotoxic agents, asparaginase products, and biotherapy administered between January 1, 2014, and December 31, 2017. In the analysis, orders that could be rounded down to the nearest vial size by 5 or 10% were included. Medication pricing information was based on wholesale acquisition cost (WAC) and was provided by the Department of Pharmacy. Cost savings per medication were determined by multiplying the WAC of the medication by the number of vials saved.
RESULTS
Over a 4-year span, 347 patients were evaluated and 552 out of a possible 3110 orders (17.7%) met criteria for a theoretical cost savings of approximately $1,126,000 (∼$3200 per patient). Rounding down doses by up to 5% resulted in a potential savings of about $529,000. When rounding was extended to 5-10% of the originally ordered dose, an additional $597,000 of approximate cost savings could have been realized. The medications with the largest impact on cost savings were rituximab, pegaspargase, and erwinia asparaginase.
CONCLUSIONS
For pediatric oncology patients, there exists a unique potential cost savings opportunity if doses are rounded down within 5 or 10% of the originally ordered weight-based or body surface area-calculated dose.
Topics: Humans; Cost Savings; Retrospective Studies; Child; Antineoplastic Agents; Drug Costs; Child, Preschool; Female; Neoplasms; Asparaginase; Cost-Benefit Analysis; Male; Biological Therapy; Adolescent; Pharmacy Service, Hospital; Hospitals, Pediatric
PubMed: 37350075
DOI: 10.1177/10781552231184583 -
Clinical Lymphoma, Myeloma & Leukemia Aug 2023L-asparaginase-based chemotherapy regimens are effective for treating chemotherapy-resistant natural killer- (NK-) cell neoplasms. To treat these lymphoma subtypes in...
INTRODUCTION
L-asparaginase-based chemotherapy regimens are effective for treating chemotherapy-resistant natural killer- (NK-) cell neoplasms. To treat these lymphoma subtypes in Asia, where NK/T-cell lymphomas are more prevalent, the NK-Cell Tumor Study Group developed the SMILE regimen, which includes a steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide. In the US however, the only commercially available form of asparaginase is the pegylated form (PEG-asparaginase) which has been incorporated into a modified SMILE (mSMILE). We sought to study the toxicity associated with replacing L-asparaginase with PEG-asparaginase in mSMILE.
PATIENTS AND METHODS
We retrospectively identified all adult patients treated with the mSMILE chemotherapy regimen in our database at Moffitt Cancer Center (MCC) between December 1, 2009, and July 30, 2021. Patients were included if they were treated with mSMILE irrespective of their underlying diagnosis. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The rate of toxicity in our mSMILE treatment group was numerically compared to data published in a metanalysis of the SMILE regimen's toxicity (Pokrovsky et al., 2019).
RESULTS
A total of 21 patients were treated with mSMILE at MCC during the 12-year analysis window. Compared to patients receiving the L-asparaginase-based SMILE, patients receiving mSMILE experienced grade 3 or 4 leukopenia less often, with a toxicity rate of 62% (median with SMILE, 85% [95% CI, 74%-95%]); thrombocytopenia, however, was more common, with a toxicity rate of 57% (median with SMILE, 48% [95% CI, 40%-55%]). Other hematological, hepatic and coagulation related toxicities were also reported.
CONCLUSION
In a non-Asian population, the mSMILE regimen with PEG-asparaginase is a safe alternative to the L-asparaginase-based SMILE regimen. There is a comparable risk of hematological toxicity, and no treatment-related mortality was seen in our population.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Lymphoma, Extranodal NK-T-Cell; Polyethylene Glycols; Retrospective Studies; Thrombocytopenia
PubMed: 37210271
DOI: 10.1016/j.clml.2023.04.005 -
Leukemia & Lymphoma 2023
Topics: Child; Humans; Pregnancy; Female; Asparaginase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polyethylene Glycols; Antineoplastic Agents
PubMed: 37516923
DOI: 10.1080/10428194.2023.2239406 -
Toxicology and Applied Pharmacology Apr 2024Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute...
Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute lymphoblastic leukemia among children and adolescents. The toxicological mechanism of AAP is not yet clear, and there are no effective preventive and treatment measures available clinically. Fibroblast growth factor 21 (FGF21) is a secretory hormone that regulates lipid, glucose, and energy metabolism balance. Acinar tissue is the main source of pancreatic FGF21 protein and plays an important role in maintaining pancreatic metabolic balance. In this study, we found that the decrease of FGF21 in pancreas is closely related to AAP. Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. The specific expression of FGF21 in the acinar tissue of AAP rats was significantly downregulated. Asparaginase caused dysregulation of the ATF4/ATF3/FGF21 axis in acinar tissue or cells, and thus mediated the decrease of FGF21. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.
Topics: Animals; Fibroblast Growth Factors; Asparaginase; Pancreatitis; Male; Rats; Pancreas; Mice; Rats, Sprague-Dawley; Polyethylene Glycols; Antineoplastic Agents; Activating Transcription Factor 4; Mice, Inbred C57BL; eIF-2 Kinase
PubMed: 38582373
DOI: 10.1016/j.taap.2024.116920 -
BMC Health Services Research Jan 2024The high costs of innovative anticancer drugs hinder a number of cancer patients' access to these drugs in China. To address this problem, in 2018, the medical insurance...
BACKGROUND
The high costs of innovative anticancer drugs hinder a number of cancer patients' access to these drugs in China. To address this problem, in 2018, the medical insurance access negotiation (MIAN) policy was implemented, when the prices of 17 innovative anticancer drugs were successfully negotiated and they were therefore included in the reimbursement list. This study aimed to explore the impact of the MIAN policy on the utilization of innovative anticancer drugs.
METHODS
With monthly data on drug expenditures and defined daily doses (DDDs) of each innovative anticancer drug from January 2017 to December 2019, interrupted time series analysis was employed to estimate both the instant (change in the level of outcome) and long-term (change in trends of outcomes) impacts of the MIAN policy on drug utilization in terms of drug expenditures and DDDs. Our sample consists of 12 innovative anticancer drugs.
RESULTS
From January 2017 to December 2019, the monthly drug expenditures and DDDs of 12 innovative anticancer drugs increased by about 573% (from US$8,931,809.30 to US$51,138,331.09) and 1400% (from 47,785 to 668,754), respectively. Overall, the implementation of the MIAN policy led to instant substantial increases of US$8,734,414 in drug expenditures and 158,192.5 in DDDs. Moreover, a sharper upward trend over time was reported, with increases of US$2,889,078 and 38,715.3 in the monthly growth rates of drug expenditures and DDDs, respectively. Regarding individual innovative anticancer drugs, the most prominent instant change and trend change in drug utilization were found for osimertinib, crizotinib, and ibrutinib. In contrast, the utilization of pegaspargase was barely affected by the MIAN policy.
CONCLUSIONS
The MIAN policy has effectively promoted the utilization of innovative anticancer drugs. To ensure the continuity of the effects and eliminate differentiation, supplementary measures should be carried out, such as careful selection of drugs for medical insurance negotiations, a health technology assessment system and a multichannel financing mechanism.
Topics: Humans; Negotiating; Interrupted Time Series Analysis; Health Expenditures; Antineoplastic Agents; Insurance; China; Drug Costs; Nitrosamines
PubMed: 38233857
DOI: 10.1186/s12913-023-10393-y -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Feb 2024To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal...
To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) . A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined. After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly (<0.001) between the POD<24 group (=14) and the POD≥24 group (=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4-6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively (=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.
Topics: Humans; Lymphoma, Extranodal NK-T-Cell; Retrospective Studies; Neoplasm Staging; Prognosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38604793
DOI: 10.3760/cma.j.cn121090-20230726-00029 -
Cureus Jan 2024Acute lymphoblastic leukemia (ALL) during pregnancy necessitates treatment with high-dose chemotherapy, which can threaten the lives of both the mother and fetus. The...
Acute lymphoblastic leukemia (ALL) during pregnancy necessitates treatment with high-dose chemotherapy, which can threaten the lives of both the mother and fetus. The aim of the treatment not only focuses on selecting and administering optimal chemotherapy with appropriate doses to the mother but also reflects the crucial understanding of the fetal gestational age at the time of administration of chemotherapy to minimize fetal exposure. We describe the case of a 19-year-old patient diagnosed with ALL at 29 weeks gestation. She received treatment in the third trimester with the Berlin-Frankfurt-Munster (BFM) 2000 induction chemotherapy protocol consisting of a combination of daunorubicin, vincristine, pegaspargase, prednisolone, and intrathecal (IT) methotrexate and gave birth to a healthy baby girl via vaginal delivery four weeks after initiating the induction of chemotherapy.
PubMed: 38371059
DOI: 10.7759/cureus.52489 -
Journal of Pharmaceutical and... Sep 2024Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological...
Improved HPLC method with automated pre-column sample derivatisation for serum pegylated L-asparaginase activity measurement in paediatric acute lymphoblastic leukaemia patients.
Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100 mm, 2.7 µm analytical column. System flow rate was optimised to 2.0 mL/min with 40×10/bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1 % o-phthaldialdehyde, 0.8 % 2-mercaptoethanol, 7.13 % methanol, and 1.81 % sodium tetraborate. The pre-column derivatisation program mixed 0.1 µL sample with 25 µL OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15 min, with L-aspartic acid eluted at 0.96 min and internal standard at 4.7 min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15 %, 3.05 %, and 3.09 % (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41 %, -1.37±3.04 %, and -3.03±3.02 % (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application.
Topics: Asparaginase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Humans; Chromatography, High Pressure Liquid; Child; Polyethylene Glycols; Drug Monitoring; Antineoplastic Agents; Reproducibility of Results; Chromatography, Reverse-Phase; Calibration
PubMed: 38843612
DOI: 10.1016/j.jpba.2024.116243 -
Journal of Pediatric Hematology/oncology Mar 2024Asparaginases are a mainstay treatment for pediatric acute lymphoblastic leukemia (ALL). Recent reports identified hypoglycemia associated with asparaginases. Other...
BACKGROUND
Asparaginases are a mainstay treatment for pediatric acute lymphoblastic leukemia (ALL). Recent reports identified hypoglycemia associated with asparaginases. Other reports describe hypoglycemia associated with 6-mercaptopurine (6-MP), another fundamental ALL therapy. Little is known about the risk of hypoglycemia associated with ALL therapy, an adverse event that puts children at risk of decreased level of consciousness, seizures, and possibly negative neurocognitive sequelae.
METHODS
We performed a retrospective chart review of 6 children with hypoglycemia during ALL treatment in our institution from May 2016 to August 2019. Timing and duration of hypoglycemia relative to polyethylene glycol (PEG)-asparaginase, 6-MP, and corticosteroids were determined. Laboratory values of the critical sample were collected.
RESULTS
The median age was 2.75 (interquartile range: 1.88 to 3.63) years. Three patients had trisomy 21. The onset of hypoglycemia was 5 to 19 days after the most recent PEG-asparaginase administration or 6 to 7 months after initiating daily 6-MP. Sixteen hypoglycemic events were documented, and 9/16 had a critical sample drawn. Six events were hypoketotic, associated with PEG-asparaginase. Three were ketotic, associated with 6-MP. Two patients required treatment with diazoxide and cornstarch.
CONCLUSIONS
Hypoglycemia associated with PEG-asparaginase occurred later and lasted longer than previous reports with l-asparaginase, with the likely mechanism being hyperinsulinism. 6-MP was associated with ketotic hypoglycemia.
Topics: Humans; Child; Child, Preschool; Asparaginase; Mercaptopurine; Retrospective Studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polyethylene Glycols; Hypoglycemia
PubMed: 38411659
DOI: 10.1097/MPH.0000000000002818