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Hematology. American Society of... Dec 2022Chemotherapy-induced thrombocytopenia (CIT) is common, resulting in increased bleeding risk and chemotherapy delays, dose reduction, and treatment discontinuation, which... (Review)
Review
Chemotherapy-induced thrombocytopenia (CIT) is common, resulting in increased bleeding risk and chemotherapy delays, dose reduction, and treatment discontinuation, which can negatively affect oncologic outcomes. The only agent approved by the US Food and Drug Administration to manage CIT (oprelvekin) was voluntarily withdrawn from the market by the manufacturer, leaving few options for patients. Therefore, patients experiencing CIT present a significant clinical challenge in daily practice. The availability of thrombopoietin receptor agonists has led to formal clinical trials describing efficacy in CIT as well as a rather extensive body of published observational data from off-label use in this setting but no formal regulatory indications for CIT to date. The accumulated data, however, have affected National Comprehensive Cancer Network guidelines, which now recommend consideration of TPO-RA clinical trials as well as off-label use of romiplostim. This review article details the evidence to date for the management of CIT with thrombopoietin receptor agonists (TPO-RAs), discussing the efficacy data, the specific circumstances when treatment is warranted (and when it is generally unnecessary), and safety considerations. Specific recommendations regarding patient selection, initiation, dosing, titration, and discontinuation for TPO-RA therapy in CIT are given, based on published data and expert opinion where evidence is lacking.
Topics: Humans; Receptors, Thrombopoietin; Thrombopoietin; Thrombocytopenia; Hemorrhage; Recombinant Fusion Proteins; Antineoplastic Agents; Purpura, Thrombocytopenic, Idiopathic; Hydrazines; Benzoates
PubMed: 36485134
DOI: 10.1182/hematology.2022000374 -
Drug Safety Nov 2014Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection,... (Review)
Review
Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 20 approved cytokine preparations (18 different cytokines; 3 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon, platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) families. In the hematopoietin family, approved cytokines are aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings.
Topics: Cytokines; Drug Approval; Humans; Recombinant Proteins
PubMed: 25270293
DOI: 10.1007/s40264-014-0226-z -
Mediterranean Journal of Hematology and... 2017Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct... (Review)
Review
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.
PubMed: 28293407
DOI: 10.4084/MJHID.2017.019 -
Oncology (Williston Park, N.Y.) Sep 2000Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is... (Review)
Review
Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is the major dose-limiting hematologic toxicity, especially in the treatment of potentially curable malignancies such as leukemia, lymphomas, and pediatric cancers. This is becoming increasingly important given the recent trend toward the use of dose-intensive combination chemotherapy regimens facilitated by supportive hematopoietic colony-stimulating factors to prevent chemotherapy-induced febrile neutropenia. The standard preventive measure against chemotherapy-induced depression of platelets in subsequent treatment cycles has been dose reduction and/or dose delay. However, follow-up data from studies in various populations of patients with cancer suggest a correlation between delivery of lower than intended doses and poor outcomes, including reduced disease-free periods and overall survival. Other consequences of thrombocytopenia include the need for platelet transfusions and subsequent exposure to the risk of numerous complications, including bacterial and viral infections; febrile, nonhemolytic transfusion reactions; and transfusion-induced immunosuppression. Furthermore, a large proportion of multitransfused patients become refractory to subsequent infusions. Refractoriness to platelet transfusions is quickly becoming more prominent. The availability of a platelet growth factor--recombinant human interleukin-11(rhIL-11, also known as oprelvekin [Neumega])--provides an effective means of preventing chemotherapy-induced thrombocytopenia and accelerating platelet recovery, thereby facilitating the administration of full doses of chemotherapy during subsequent cycles and avoiding the need for rescue with platelet transfusions.
Topics: Antineoplastic Agents; Bone Marrow; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunosuppression Therapy; Interleukin-11; Maximum Tolerated Dose; Neoplasms; Opportunistic Infections; Platelet Transfusion; Recombinant Proteins; Survival Rate; Thrombocytopenia
PubMed: 11033835
DOI: No ID Found -
Cleveland Clinic Journal of Medicine May 2004Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin... (Review)
Review
Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment.
Topics: Anemia; Antiviral Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Interleukin-11; Neutropenia; Patient Compliance; Polyethylene Glycols; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin; Thrombocytopenia
PubMed: 15468613
DOI: 10.3949/ccjm.71.suppl_3.s17 -
Oncology (Williston Park, N.Y.) Sep 2000
Review
Topics: Antineoplastic Agents; Blood Platelets; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Hematopoiesis; Humans; Interleukin-11; Maximum Tolerated Dose; Megakaryocytes; Recombinant Proteins; Thrombocytopenia
PubMed: 11033833
DOI: No ID Found -
Annals of Palliative Medicine Aug 2022Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing...
BACKGROUND
Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system.
METHODS
We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed.
RESULTS
A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO.
CONCLUSIONS
In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Hematologic Neoplasms; Humans; Interleukin-11; Platelet Count; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Thrombopoietin
PubMed: 36064361
DOI: 10.21037/apm-22-880 -
Oncology (Williston Park, N.Y.) Sep 2000Placebo-controlled clinical trials of recombinant human interleukin-11 (rhIL-11, also known as oprelvekin [Neumega]) in patients with nonmyeloid malignancies have... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Placebo-controlled clinical trials of recombinant human interleukin-11 (rhIL-11, also known as oprelvekin [Neumega]) in patients with nonmyeloid malignancies have demonstrated significant efficacy in preventing postchemotherapy platelet nadirs of < or = 20,000/microL, and reducing the need for platelet transfusions while continuing chemotherapy without dose reductions. The likelihood of requiring a platelet transfusion in rhIL-11-treated patients receiving chemotherapy is approximately 40% lower than the risk for untreated patients. Treatment with rhIL-11 appears to accelerate earlier recovery to platelet counts of 20,000/microL, 50,000/microL, and 100,000/microL, suggesting that patients treated with rhIL-11 are more likely to be able to receive their next chemotherapy cycle in a timely fashion. rhIL-11 shows sustained efficacy over multiple cycles of full-dose chemotherapy. Activity has also been demonstrated in pediatric patients with solid tumors. The use of rhIL-11 in combination with granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) may also produce a synergistic hematopoietic effect, resulting in earlier neutrophil recovery. The recommended adult dose regimen for rhIL-11 is 50 micrograms/kg administered subcutaneously once daily beginning 6 to 24 hours after the administration of chemotherapy until a postnadir platelet count of > or = 50,000/microL is reached. The recommended pediatric dose of rhIL-11 is 75 micrograms/kg subcutaneously, once daily beginning 6 to 24 hours after the administration of chemotherapy until a postnadir platelet count of > or = 50,000/microL is reached. The administration of rhIL-11 for greater than 21 days has not been studied and therefore is not recommended.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Bone Marrow; Breast Neoplasms; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Humans; Interleukin-11; Middle Aged; Recombinant Proteins; Thrombocytopenia; Treatment Outcome
PubMed: 11033836
DOI: No ID Found