Dr Sarita Retief helps us understand what neutropenia is, how chemotherapy causes it and the treatment options of G-CSF.
One of the major side effects of chemotherapy is the fact that the production of cells in the bone marrow can be suppressed. This can cause lowering of the red blood cells (anaemia), white blood cells (neutropenia) and the platelets (thrombocytopenia). Production of all these cell lines are affected differently (in different degrees and at different times) by the various types of chemotherapy regimes.
What are neutrophils?
Neutrophils are a subgroup of the white cells and forms about 45-75% of the total white cells. Their main responsibility is to fight bacterial infections. The normal value of neutrophils in the blood is 1500-8000 neutrophils/ul. When the absolute neutrophil count (ANC) drops to below 500/ul, it is considered to be severe, and the patient is at high-risk of developing a serious and sometimes life-threatening infection, called neutropenic sepsis.
The risk of developing a severely low ANC, depends on several factors:
1. The type and dosing of chemotherapy is the main determining factor. A risk classification, dividing the different chemotherapies in different classes of risk, was developed:
- Risk for developing neutropenia > 20%: includes among others, dose dense chemotherapy for breast cancer and docetaxel/gemcitabine for sarcomas.
- Risk of developing neutropenia 10-20%.
- Risk of developing neutropenia < 10%. In this group, the risk for neutropenia is very low.
2. The age and general health of the patient.
3. Concomitant radiation.
4. Exposure to previous toxic agents to the bone marrow.
Granulocyte colony-stimulating factor (G-CSF)
Medication has been developed to reduce the degree and duration of neutropenia, and therefore the risk of severe infections. These are called recombinant human granulocyte colony-stimulating factor (G-CSF) (filgrastim and pegylated filgrastim) and granulocyte-macrophage colony stimulating factor (GM-CSF) (sargramostim; not available in SA yet).
These drugs stimulate the production, maturation and activation of neutrophils. There is also medication that can increase red blood cells, but nothing to increase platelets during chemotherapy.
When do we use G-CSF?
- Primary prophylaxis. This is when it’s given from the beginning of treatment after every chemotherapy cycle, to prevent neutropenia.
- Secondary prophylaxis. Here we wait for one incidence of low white cells to occur, and then give it after consequent cycles of chemotherapy. This is mainly how it’s used in the cost constraint environment in SA.
- It’s generally not recommended in established neutropenia with fever.
It must be given at least 24-72hr after cessation of the chemotherapy and about two weeks before the next chemotherapy. If given outside of this timeframe, the newly formed white cells will also be destroyed by the chemotherapy.
What formulations are available in SA?
Filgrastim: (30MU and 48MU prefilled syringes). There is the original drug and two biosmilar drugs available. You need to use these drugs daily until the neutrophils recovered after their lowest value. It can take five to seven days or even longer.
Pegfilgrastim is a pegylated form of filgrastim, meaning that it’s in a slow-release form. A pegfilgrastim biosimilar has recently been launched in SA. You only have an injection 24hrs after chemotherapy, which would be sufficient to stimulate the neutrophils.
All these options can do the job, but they differ in convenience and price. It’s up to your treating doctor to decide which one would be the best for you.
How are G-CSF given?
Filgrastim and pegfilgrastim is available in ready to use, single use syringes that must be kept in the fridge. They are given as a subcutaneous injection in the upper arm, abdomen at least 5cm from the navel, front middle thigh or upper outer buttock. It’s important to rotate the area of injection. It’s usually self-administered or someone can help you with the injection.
Side effects include bone pain, fever, cough, back pain, nausea, skin rash, fatigue and allergies. These are all manageable. There are also very rare effects like aortitis (inflammation of the aorta), vasculitis, respiratory distress syndrome and rupture of the spleen.
Some observational studies even suggested that there is a small, but real increased risk of therapy related bone marrow cancers. Most of these symptoms can also be related to the chemotherapy that is used.
It’s important to understand that this group of drugs can’t be used indiscriminately. They have changed the way we give chemotherapy, they have lowered side effects, and we can cure more patients. But they do have side effects and need to be given under the supervision of a doctor experienced in their use.
MEET THE EXPERT – Dr Sarita Retief
Dr Sarita Retief is currently working as a clinical and radiation oncologist at Nelspruit Mediclinic in the private sector. She completed pre- and post-graduate studies at the University of the Free State.