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26 Cards in this Set
- Front
- Back
Describe the pharmacology of Colony-stimulating Factor
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Pluripotent Hemopoietic stem cells differentiate into Lymphoid Progenitor cells (NK, T, B cells) and Myeloid Progenitor Cells.
Myeloid Progenitor Cells, using GM-CSF and other cytokines differentiate into: Erythroid Progenitor Cells Megakaryocytes Basophil Progenitor Cells Eosinophil Progenitor Cells Granulocyte-monocyte Progenitor Cells |
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Continuation
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Erythroid Progenitor Cells (Turn into Erythrocytes via Erythropoietin)
Megakaryocytes (Bud off Platelets via thrombopoeitin Basophil Progenitor Cells (Turn into Basophils) Eosinophil Progenitor Cells (Turn into Eosinophils) Granulocyte-monocyte Progenitor Cells (Turn into Neutrophils via G-CSF and Monocytes via M-CSF) So, G-CSF has more narrow effects than GM-CSF |
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Continuation
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CSF's increase Neutrophil Production, Maturation, Activation and Migration
Administration of CSF increases Neutrophil counts, decrease trough Neutrophil counts during chemotherapy in comparison to no CSF administered. |
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What are the indications for Primary Prophylaxis use of CSFs
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If the regimen's risk of febrile neutropenia is > 20%
If the regimen's risk of febrile neutropenia is 10-20% and one of the following: Age > 65 Pre-existing neutropenia Poor performance status Impaired renal or hepatic function Extensive prior chemotherapy Poor nutrition Active Infection |
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Continuation
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Dose dense therapy when supported by clinical evidence.
Dose dense therapy - a strategy for giving chemotherapy cycle faster than you normally would. Giving stimulating agents may allow this. This is appropriate for certain patients. CHOP-14 (standard for non-Hodgkin's lymphoma given every 14 days) CHOP-21 Mobilize Peripheral Blood Stem Cells in preparation of Autologous Stem Cell Transplant (Higher doses) |
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Risk <10 % - not a candidate, but now....
After 3 days of antibiotics, patient is still febrile/neutropenic. Is CSF indicated now? |
Controversial - risk factors need to be present
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What are the risk factors that need to be present for this to be indicated?
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One of these:
Sepsis Age >65 ANC < 100 or expected length > 10 days Pneumonia Invasive fungal infection Hospitalization at time of fever Prior episode of FN |
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What options are available for decreasing the risk of FN in the future going forward?
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Dose reduction
Alternative regimen Secondary prophylaxis |
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Name the available Growth Factors
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G-CSF
-Filgastim 5 mcg/kg (round to 300 mcg or 480 mcg vial size) SC daily - Do not give in period of 24 hours before to 24 hours after chemotherapy Pegfilgrastim 6 mg SC once -Pegylation provides prolonged effect due to reduced clearance - Do not give in period of 14 days before to 24 hr after chemotherapy |
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Why can't you give these agents the day of chemotherapy?
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Chemotherapy kills rapidly dividing cells.
These agents increase the rate of neutrophil production, so if given concomitantly you will actually do harm to the patient as the chemo will kill the rapidly dividing neutrophils |
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Continuation of available agents
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GM-CSF
-Sargramostim 250 mg/m^2 SC daily -Do not give in a period of 24 hours before to 24 hours after chemotherapy |
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How do you select which agent to use?
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There are few comparative trials
Cost: Filgrastim (G-CSF), Sargramostim (GM-CSF) 200-300 dollars per dose Pegfilgrastim 2000-3000 per dose GM-CSF > G-CSF adverse effects |
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What are the adverse effects of these agents?
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Bone pain
Fever Diarrhea Nausea Rash Edema Injection site pain Effusions |
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When do you stop therapy?
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Resolution of Neutropenia
ANC > 10,000 ANC > 1000 x 3 days whichever comes first |
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Overview of chemotherapy induced anemia.
This is controversial. Guidelines aren't clear. In mild malignancies this is controversial. |
Anemia occurs in 30-90 percent of cancer patients.
Causes include bleeding, hemolysis, marrow infiltration of tumor Chemo toxicity to RBC precursors Chemo induced nephrotoxicity Symptoms: Fatigue, Syncope, Chest Pain |
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How do you manage anemia?
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Evaluate iron deficiency (don't have to know ferritin, transferrin sat values)
--> PRBC Transfusion or ESA Administration |
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What are the indications for ESA therapy in cancer patients?
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Myelodysplastic syndrome
Patients with CIA who are receiving palliative chemotherapy for non-myeloid malignancies (Not recommend for curative disease) - Treatment period can continue ONLY up to 6 weeks following chemotherapy |
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When a patient is done with chemotherapy and they are still anemic, can they now receive ESA?
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No, still not a candidate
Only while you are getting chemotherapy. |
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If the patient now has metastatic incurable ovarian cancer? Is she now a candidate?
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Yes
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What ESA's are available?
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Epoetin alfa 40,000 units SC once weekly
Darbepoetin 500 mcg SC every 3 weeks |
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How do you monitor these agents?
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Cannot start these agents if Hgb > 10!!!
Monitor Hg levels weekly Initial response requires at least 2 weeks Reduce dose if Hg increases > 1g/dL in a 2 week period Increase dose if no response in 4 weeks Discontinue when Hg reaches goal of avoiding transfusions, or no response after 8 weeks Transfusion is your treatment in acute situations. These agents take a while to work. |
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What are the adverse effects of these agents?
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Decreases survival (mostly when Hg > 12 g/dL)
Increased thrombosis Time to tumor progression shortened Hypertension Seizures ESA neutralizing antibodies (causing pure red cell aplasia - mostly in europe with a different formulation but has happened here) |
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Summary graph
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Shows that targeting Hg > 12 there are bad outcomes. Patients died faster.
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What are the benefits?
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Transfusion avoidance
-Transfusion reactions, viral transmission, iron overload, thrombotic events |
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What is REMS?
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Risk Evaluation and Mitigation Strategy
REMS program for these agents is called ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) Provider must go online, complete training program, and then each patient must be counseled on the risk and benefits of ESAs and an acknowledgement form must be signed. |
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Fact:
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Medicare only covers this if Hg < 10 g/dL prior to any dose.
All the guidelines say over 10 is okay, but it won't be paid for. |