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Journal of Feline Medicine and Surgery Aug 2022The aim of this retrospective study was to determine the response to a single injection of pegylated asparaginase ('pegaspargase') and to assess the tolerability and...
OBJECTIVES
The aim of this retrospective study was to determine the response to a single injection of pegylated asparaginase ('pegaspargase') and to assess the tolerability and outcome of prolonged incorporation of pegaspargase into a modified COP (cyclophosphamide, vincristine, prednisolone) regimen in pegaspargase sensitive cats.
METHODS
Fifty-six client-owned cats with confirmed macroscopic high-grade lymphoma at any anatomical site were included. Treatment was commenced with a single pegaspargase injection. Cats showing an objective response were eligible to continue therapy with pegaspargase incorporated into a modified COP protocol and had their survival analysed using the Kaplan-Meier method and log-rank test.
RESULTS
Objective response to pegaspargase was reported in 46 cats (82%), including 21 (38%) complete and 25 (44%) partial responses. Thirty-four responders continued therapy with pegaspargase-COP as the first-line treatment. Of these, 31 cats (92%) achieved complete remission with a median duration of the first remission (disease-free survival [DFS]) of 816 days. The median overall survival time (OST) for all 34 cats treated with pegaspargase-COP was 181 days. Response to the initial pegaspargase injection before COP initiation was significantly associated with DFS ( = 0.04) and OST ( = 0.001). Median DFS/OST for cats with complete response to initial pegaspargase injection was significantly longer compared with those with partial remission (>1273 days/>2066 days vs 77 days/108 days, respectively). Cats with gastric lymphoma showed a significantly longer survival (OST 854 days, 1- and 2-year survival rate 57.1%) compared with cats with intestinal lymphoma (OST 102 days, 1-year survival rate 0%). The pegaspargase-COP protocol was generally well tolerated, but two deaths were likely attributable to treatment-related toxicity during the maintenance phase. Importantly, none of the cats experienced hypersensitivity, despite multiple repeated treatments with pegaspargase.
CONCLUSION AND RELEVANCE
Pegaspargase is an effective agent for feline lymphoma. Its incorporation into a COP chemotherapy protocol may confer a survival benefit, especially in cats with complete response to pegaspargase. Treatment is generally well tolerated, but careful monitoring is recommended. Further studies are required to assess the benefits of pegaspargase as monotherapy or as part of different multi-agent chemotherapy regimens.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cat Diseases; Cats; Cyclophosphamide; Lymphoma; Lymphoma, Non-Hodgkin; Polyethylene Glycols; Retrospective Studies
PubMed: 35748790
DOI: 10.1177/1098612X221101533 -
Annals of Hematology Jan 2019Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we...
Gemcitabine, cisplatin, and dexamethasone (GDP) in combination with methotrexate and pegaspargase is active in newly diagnosed peripheral T cell lymphoma patients: a phase 2, single-center, open-label study in China.
Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL. Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML chemotherapy every 28 days. After 4 cycles, responding patients continued to receive either autologous stem cell transplantation or the MTX/cytarabine (MA) regimen for consolidation. This trial is registered with www.chictr.org.cn (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow-up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months, and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS was only 8 months. The main adverse event was hematologic toxicity: 50% patients showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL patients is an effective induction regimen compared with standard CHOP, and the toxicity was more significant but acceptable. However, future studies exploring new drug combinations are warranted to overcome relapse after remission. ClinicalTrials.gov Identifier: NCT02987244.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; China; Cisplatin; Deoxycytidine; Dexamethasone; Disease-Free Survival; Female; Follow-Up Studies; Humans; Lymphoma, T-Cell, Peripheral; Male; Methotrexate; Middle Aged; Polyethylene Glycols; Survival Rate; Gemcitabine
PubMed: 30209556
DOI: 10.1007/s00277-018-3488-1 -
Cancer Management and Research 2018l-asparaginase or pegaspargase-based chemotherapies have shown promising results in the treatment of extranodal NK/T-cell lymphoma. A retrospective study was conducted...
Pegaspargase, gemcitabine, dexamethasone, and cisplatin (P-GDP) combined chemotherapy is effective for newly diagnosed extranodal NK/T-cell lymphoma: a retrospective study.
PURPOSE
l-asparaginase or pegaspargase-based chemotherapies have shown promising results in the treatment of extranodal NK/T-cell lymphoma. A retrospective study was conducted to determine the efficacy and safety of pegaspargase, gemcitabine, dexamethasone, and cisplatin (P-GDP) combined chemotherapy in patients with newly diagnosed extranodal NK/T-cell lymphoma.
PATIENTS AND METHODS
From September 2013 to November 2016, 57 patients with newly diagnosed, stages I to IV, extranodal NK/T-cell lymphoma received P-GDP chemotherapy. Clinical data from these patients were collected and analyzed to evaluate the efficacy and safety of P-GDP.
RESULTS
All patients were subjected to 1-6 cycles of P-GDP chemotherapy, and the median number of cycles of P-GDP regimen administered was 3. The overall response rate was 89.5% (51/57), including a complete response rate of 70.2% (40/59) and a partial response rate of 19.3% (11/57). The median follow-up time was 28 months (range 2-54 months). The 2-year overall survival and progression-free survival (PFS) rates were 82.9% and 75.9%, respectively. For stage I/II patients and stage III/IV patients, 2-year PFS were 80.8% and 66.7%, respectively. The most common grade 3/4 adverse events were neutropenia (42.1%), thrombocytopenia (38.6%), and hypofibrinogenemia (26.3%). No treatment-related deaths were observed.
CONCLUSION
P-GDP combination chemotherapy is highly effective and safe for newly diagnosed patients with extranodal NK/T-cell lymphoma, nasal type. Additional large sample prospective trials are required to confirm these results.
PubMed: 30464606
DOI: 10.2147/CMAR.S179567 -
Bulletin Du Cancer Nov 2022Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute...
[Prevention and management of pegaspargase associated-toxicities (excluding coagulation abnormalities). Recommendations of the French Society of Children and Adolescent Cancers (Leukemia committee)].
Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Its particular toxicity profile requires a specific management to improve safety and tolerability and optimize treatment outcome and therefore survival. Within the framework of workshops of practice harmonization of the French Society of Children and Adolescent Cancers, diagnostic and management of the most commonly occuring toxicities (excluding coagulation abnormalities) during Pegaspargase treatment were reviewed according to the analysis of published studies.
Topics: Adult; Humans; Adolescent; Child; Asparaginase; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome; Blood Coagulation Disorders; Antineoplastic Agents
PubMed: 35987855
DOI: 10.1016/j.bulcan.2022.06.004 -
Chinese Medical Journal Mar 2023
Topics: Humans; Gemcitabine; Etoposide; Dexamethasone; Lymphoma, T-Cell; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Neoplasm Staging; Lymphoma, Extranodal NK-T-Cell
PubMed: 36939235
DOI: 10.1097/CM9.0000000000002570 -
Journal of Clinical Oncology : Official... Mar 2020In the DCOG ALL-11 protocol, polyethylene glycol-conjugated asparaginase (PEGasparaginase) and asparaginase treatment of pediatric acute lymphoblastic leukemia are...
PURPOSE
In the DCOG ALL-11 protocol, polyethylene glycol-conjugated asparaginase (PEGasparaginase) and asparaginase treatment of pediatric acute lymphoblastic leukemia are individualized with therapeutic drug monitoring (TDM). The efficacy of TDM and its effect on asparaginase-associated toxicity are reported.
PATIENTS AND METHODS
After induction with 3 fixed intravenous doses of 1,500 IU/m PEGasparaginase, medium-risk patients (n = 243) received 14 individualized doses that targeted trough levels of 100-250 IU/L, standard-risk patients (n = 108) received 1 individualized dose, and high-risk patients (n = 18) received 2-5 fixed administrations (1,500 IU/m). After a neutralizing hypersensitivity reaction, patients were started with 20,000 IU/m asparaginase 3 times per week, and l-asparagine was measured to monitor asparaginase efficacy. Several asparaginase-associated toxicities were studied.
RESULTS
The final median PEGasparaginase dose was lowered to 450 IU/m. Overall, 97% of all trough levels of nonallergic patients were > 100 IU/L. Asparagine was < 0.5 μM in 96% and 67% of the PEGasparaginase and asparaginase levels > 100 IU/L, respectively. Ten percent developed a neutralizing hypersensitivity reaction to PEGasparaginase, of which 40% were silent inactivations. The cumulative incidence of grade 3-4 pancreatitis, central neurotoxicity, and thromboses was 12%, 4%, and 6%, respectively, and not associated with asparaginase activity levels. During medium-risk intensification, 50% had increased ALT and 3% hyperbilirubinemia (both grade 3/4 and correlated with asparaginase activity levels), and 37% had grade 3/4 hypertriglyceridemia. Hypertriglyceridemia occurred less in intensification compared with ALL-10 (37% 47%), which is similar to ALL-11 but with higher asparaginase levels during intensification.
CONCLUSION
TDM of asparaginase results in a significant reduction of the PEGasparaginase dose with adequate asparaginase activity levels and sufficient asparagine depletion. In addition, with TDM, silent inactivation and allergic-like reactions were identified. However, the effect of reduced asparaginase activity levels on toxicity is limited.
Topics: Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Hypersensitivity; Humans; Polyethylene Glycols; Precision Medicine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic
PubMed: 31922920
DOI: 10.1200/JCO.19.02292 -
The Journal of Pediatric Pharmacology... 2022The purpose of this study was to evaluate the efficacy of a standardized premedication and therapeutic drug monitoring (TDM) protocol to prevent hypersensitivity...
OBJECTIVE
The purpose of this study was to evaluate the efficacy of a standardized premedication and therapeutic drug monitoring (TDM) protocol to prevent hypersensitivity reactions from pegaspargase infusions. Pegaspargase is an essential therapeutic agent used for the treatment of acute lymphoblastic leukemia (ALL) in pediatric patients.
METHODS
This study was a retrospective cohort study conducted at Wolfson Children's Hospital, Jacksonville, Florida, and included pediatric ALL patients 0 to 21 years old. Patients were excluded if they had not received the appropriate premedication after protocol implementation or had received premedication before protocol implementation. Patients were separated into 2 groups: those who received premedication before pegaspargase infusion and those who did not. The primary endpoint was the incidence of documented hypersensitivity reactions. Observational data endpoints included incidence of silent inactivation and cost savings from reducing complicated drug substitutions.
RESULTS
A total of 38 patients (50 doses in no premedication group; 80 doses in premedication group) were evaluated. There was not a significant reduction in the incidence of hypersensitivity reactions for patients receiving premedication and TDM (5.3% vs 6.4%, p = 1.0). A trend towards patients reacting earlier with more severe reactions in the post-implementation group was observed. There were no incidences of silent inactivation. Observational cost analysis predicts potential drug cost savings of $106,550.45.
CONCLUSIONS
A standardized premedication protocol did not reduce the incidence of hypersensitivity reactions. Premedication to prevent hypersensitivity reactions may provide a potential drug cost savings. Further investigation is warranted to assess the efficacy of a standardized premedication and TDM protocol to prevent hypersensitivity reactions.
PubMed: 35350153
DOI: 10.5863/1551-6776-27.3.232 -
Journal of Clinical Medicine Feb 2020Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either...
Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia.
Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA ( = 0.027). Event-free survival was significantly different in favor of HAM-pegA ( = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.
PubMed: 32079074
DOI: 10.3390/jcm9020536 -
Leukemia Research Aug 2016Extranodal nature killer (NK)/T cell lymphoma (ENKL), nasal type, is a highly aggressive and heterogeneous disease. Here we report a retrospective study of 38...
Efficacy and tolerance of pegaspargase, gemcitabine and oxaliplatin with sandwiched radiotherapy in the treatment of newly-diagnosed extranodal nature killer (NK)/T cell lymphoma.
Extranodal nature killer (NK)/T cell lymphoma (ENKL), nasal type, is a highly aggressive and heterogeneous disease. Here we report a retrospective study of 38 newly-diagnosed ENKL patients treated with pegaspargase, gemcitabine, oxaliplatin (P-Gemox) and sandwiched radiotherapy in our department during 2012-2016. A median of 4 (range, 2-6) (total=141) cycles of P-Gemox were administered. Interim restaging after at least 2 cycles showed complete remission (CR) rate of 23.68%, partial remission (PR) rate of 63.16%, giving an overall response rate (ORR) of 86.84%. On treatment completion, the ORR became 92.1% (CR=86.84%, PR=5.26%). Only one patient experienced disease progression during therapy. Multivariate analysis showed gender was a significant independent factor impacting on CR. Hematologic toxicity was common yet nonhematologic toxicity was mild, both of them can be well controlled by supportive treatments and only one treatment-related death was observed. At a median follow-up of 15.5 months, 4 patients (10.53%) experienced disease progression and died of disease. 1-year progression-free survival (PFS) rate and 1-year overall survival (OS) rate for the whole cohort were 86.7% and 86.6%. The P-Gemox regimen with sandwiched radiotherapy may be a promising option in the treatment of newly-diagnosed ENKL due to its high efficacy yet low toxicity.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Combined Modality Therapy; Deoxycytidine; Disease-Free Survival; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Polyethylene Glycols; Remission Induction; Retrospective Studies; Survival Rate; Treatment Outcome; Young Adult; Gemcitabine
PubMed: 27239738
DOI: 10.1016/j.leukres.2016.05.004 -
Annals of Hematology Nov 2023The incorporation of pediatric-inspired regimens in the adolescent-young-adult (AYA) and adult populations have resulted improved survival outcomes (Stock et al. Blood...
The incorporation of pediatric-inspired regimens in the adolescent-young-adult (AYA) and adult populations have resulted improved survival outcomes (Stock et al. Blood 133(14):1548-1559 2019; Dunsmore et al. J Clin Oncol 38(28):3282-3293 2020; DeAngelo et al. Leukemia 29(3):526-534 2015). Nonetheless incorporation of such regimens is limited by increased toxicity to asparaginase. Dosing strategies that reduce the weight-based dose of pegylated-L-asparaginase (PEG-asparaginase) utilizing activity monitoring have been shown to result in better tolerability of these regimens. The purpose of this study was to analyze the efficacy and safety of treating adults with Philadelphia chromosome negative (Ph-) ALL with pediatric-inspired regimens that incorporate PEG-asparaginase dose adjustments and asparaginase activity level monitoring. Patients aged 18-65 years initiated on pediatric-inspired regimens utilizing dose-reduced PEG-asparaginase with therapeutic drug monitoring-guided adjustments were included. The screening of 122 patients treated between 2015 and 2021 resulted in the inclusion of 54 patients. The median age of the cohort was 35 years (16-65 years), and median body mass index (BMI) was 30 kg/m (18.3-53.4 kg/m). The 36-month survival estimate was 62.1% (95% CI 48.1-77.7%), and the median overall survival (OS) was 62.2 months (95% CI 35.1-89.3 months). In the AYA cohort, the 36-month survival was 71.2% (95% CI 55.8-91%) and the median overall survival was not reached. Survival was not significantly affected by immunophenotype or BMI. Discontinuation due to toxicity or hypersensitivity reactions was low at 11% and 9% respectively. The encouraging survival outcomes and favorable tolerability of this older population in the real-world setting support the use of individualized PEG-asparaginase dosing with PharmD-guided therapeutic drug monitoring.
Topics: Adolescent; Adult; Humans; Asparaginase; Drug Monitoring; Polyethylene Glycols; Body Mass Index
PubMed: 37480389
DOI: 10.1007/s00277-023-05373-5