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26 Cards in this Set

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Describe the pharmacology of Colony-stimulating Factor
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
Continuation
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
Continuation
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.
What are the indications for Primary Prophylaxis use of CSFs
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
Continuation
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)
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
What are the risk factors that need to be present for this to be indicated?
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
What options are available for decreasing the risk of FN in the future going forward?
Dose reduction
Alternative regimen
Secondary prophylaxis
Name the available Growth Factors
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
Why can't you give these agents the day of chemotherapy?
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
Continuation of available agents
GM-CSF
-Sargramostim 250 mg/m^2 SC daily
-Do not give in a period of 24 hours before to 24 hours after chemotherapy
How do you select which agent to use?
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
What are the adverse effects of these agents?
Bone pain
Fever
Diarrhea
Nausea
Rash
Edema
Injection site pain
Effusions
When do you stop therapy?
Resolution of Neutropenia
ANC > 10,000
ANC > 1000 x 3 days
whichever comes first
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
How do you manage anemia?
Evaluate iron deficiency (don't have to know ferritin, transferrin sat values)

--> PRBC Transfusion or ESA Administration
What are the indications for ESA therapy in cancer patients?
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
When a patient is done with chemotherapy and they are still anemic, can they now receive ESA?
No, still not a candidate
Only while you are getting chemotherapy.
If the patient now has metastatic incurable ovarian cancer? Is she now a candidate?
Yes
What ESA's are available?
Epoetin alfa 40,000 units SC once weekly

Darbepoetin 500 mcg SC every 3 weeks
How do you monitor these agents?
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.
What are the adverse effects of these agents?
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)
Summary graph
Shows that targeting Hg > 12 there are bad outcomes. Patients died faster.
What are the benefits?
Transfusion avoidance
-Transfusion reactions, viral transmission, iron overload, thrombotic events
What is REMS?
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.
Fact:
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.