This is the first in a series of articles about chemotherapy. Over the next few weeks, we'll discuss what chemotherapy is, indications for chemotherapy, how we assess response to chemotherapy, how chemotherapy works, why chemotherapy stops working, what happens when you drop your dog off for chemotherapy, possible side effects and how to avoid them.
I hope these articles will increase your understanding of chemotherapy, how it works, and help ensure your dog has a good experience with treatment (if you decide to pursue chemotherapy treatment for your dog).
Remember, chemotherapy is very different in dogs than in people, so keep an open mind and make your decisions (to treat or not) based on facts. Your best bet is always to consult with a veterinary oncologist so they can discuss your dog's specific situation and provide specific recommendations.
If you have questions about an article, feel free to reach out by sending me an email at the address listed at the bottom of this article.
Strictly speaking, what is chemotherapy?
Chemotherapy involves any cancer treatment used to kill cancer cells. Chemotherapy agents typically kill rapidly dividing cells in the body by interfering with a specific phase of the cell cycle preventing DNA replication. There are many complex ways that chemotherapy drugs can kill tumor cells.
Chemotherapy agents are derived from all types of compounds. Some are derived from plants, others from antibiotics; even steroids (prednisone) count as chemotherapy, since they can induce programmed cell death (apoptosis) for many round cell tumors such as mast cell tumors, lymphoma, plasma cell tumors, etc.
What are the indications for chemotherapy?
There are quite a few situations in which an oncologist would recommend chemotherapy. These are listed below.
1 - Metastatic disease:
If a patient has metastatic disease (spread of cancer to another organ), we know that we cannot remove all cancer cells with surgery. We also know that cancer cells have access to either blood vessels or lymphatics (or both) and will continue to produce new metastatic tumors if not treated. Chemotherapy is needed because it can travel throughout the body and access all tissues/organs where cancer cells exist.
In the metastatic disease setting, chemotherapy often continues indefinitely, for as long as it is effective at slowing down cancer and as long as the patient tolerates treatment.
If chemotherapy is stopped, metastasis will progress, often rapidly, leading to a declining quality of life.
2 - Adjuvant chemotherapy:
When a tumor is surgically removed that is known to be malignant (has the potential to metastasize- spread to other organs), chemotherapy is typically recommended if the likelihood of metastasis is at least 25%.
In this scenario, there are a finite number of chemotherapy treatments recommended (based on the type of cancer diagnosed). Throughout treatment, the oncologist monitors to ensure that metastasis has not occurred. If evidence of metastasis has found before the chemotherapy protocol is finished, it means the chemotherapy treatment is not working. The oncologist would then discuss changing chemotherapy treatments; the new protocol would continue indefinitely, because now the patient has a significantly worse prognosis and will only be alive for as long as chemotherapy is effective.
3 - Neo-adjuvant chemotherapy:
There are some cases (mast cell tumors, for example) where we have a tumor that is too large to completely remove with surgery, but we feel that if we can shrink it with chemotherapy, it might become small enough to allow for a successful surgery.
For mast cell tumors, we commonly prescribe a few days of prednisone (steroid) for this, but I have also used vinblastine chemotherapy.
4 - Induction + consolidation chemotherapy:
Lymphoma is probably the most common cancer that uses a protocol involving induction and consolidation phases of treatment. In many protocols for lymphoma, we will give chemotherapy more frequently at the start of treatment to help the patient achieve a remission. Then, we will reduce the frequency of treatment to help them maintain their remission.
If a lymphoma patient achieves a remission in the induction phase and chemotherapy is stopped (we skip the consolidation phase) they will quickly come out of remission.
5 - Rescue chemotherapy:
Rescue chemotherapy protocols are used when a patient fails a first line treatment. The most common example of this is with lymphoma. Lymphoma patients are expected to achieve remission with their first protocol. We know that since a cure is not expected, these dogs will come out of remission at some point in the future. When this occurs, we can try to help them achieve a second remission using a rescue protocol. Rescue protocols typically consist of chemotherapy agents that the patient has not tried (that their cancer is hopefully not resistant to). The more times a patient comes out of remission, the more aggressive their cancer is and the more difficult it is to treat. For a lymphoma patient, the second remission is often half the length of the first, the third is half the length of the second (and so on and so forth).
6 - Palliative chemotherapy:
There are also cases where we give chemotherapy purely to improve a patient's quality of life or to decrease the signs that a patient is experiencing from their cancer. In this case, our decisions as to how to adjust/modify treatment will come from how well the patient is doing and if we are achieving our goal of improving their quality of life with treatment.
How do we assess response to chemotherapy?
When we are giving chemotherapy to kill cancer cells and shrink a tumor, we take frequent measurements to help determine how well treatment is working.
If we are treating cancer that can be measured on physical exam (a mass on a leg or a metastatic lymph node), measurements are taken at each chemotherapy treatment. If we are monitoring internal disease (an enlarged lymph node in the abdomen, cancer in the lung), we give two chemo treatments then re-evaluate every third treatment. Three-view thoracic radiographs (chest x-rays) are needed to evaluate the lungs. Abdominal ultrasound is needed to evaluate cancer in the abdomen.
If cancer goes away with treatment, this is called a complete remission. A complete remission means that there's no evidence of cancer on physical exam, x-rays or ultrasound.
If cancer decreases in volume by 50% (or tumor diameter by 30%) and no new tumors develop, this is called a partial remission. This includes the primary tumor, affected lymph nodes, lung nodules - we have to assess everywhere the patient has cancer to accurately assess response.
If tumor volume increases by at least 25% (or 20% diameter) or a new mass or metastatic nodule develops, the patient has progressive disease.
If what we're monitoring doesn't increase or decrease in size/volume by more than 20% (and new disease does not develop), this is stable disease.
**Note - lymphoma monitoring is slightly different.
The current chemotherapy protocol is typically deemed successful if disease is stable or either a complete or partial remission have been achieved. The protocol is abandoned and considered to have "failed" if progressive disease has occurred.
If progressive disease is noted, an oncologist will discuss alternative options for treatment (other chemotherapy protocols, palliative care) with the family.
Remember that if a patient achieves a complete remission, this is a complete clinical remission. It is not the same as a cure. Remission means that we cannot find any evidence of cancer on exam, x-ray, ultrasound (or CT if we were going to perform a CT scan).
For the vast majority of cancers and the vast majority of patients in a complete remission, there are still microscopic cancer cells remaining in the body which we cannot detect. Over time, these cells can survive and multiply to produce metastatic disease somewhere in the body. This is why an oncologist will recommend a monitoring regimen after surgery and after chemotherapy is completed. If/when cancer returns, we want to be able to catch it early, so we can intervene with additional therapy and help the patient live longer (and potentially achieve another remission).
How long is the typical chemotherapy protocol?
The length of chemotherapy protocols vary depending on the tumor type being treated and the tumor burden.
Tumor burden refers to whether we have metastatic disease vs microscopic disease vs a single non-resectable tumor.
If surgery has been performed to remove a tumor that is expected to metastasize (osteosarcoma for example), we recommend giving six doses of chemotherapy (some oncologists recommend four), followed by monitoring. Monitoring consists of 3-view thoracic radiographs every three months for at least 1 year post surgery, then every six months.
If we're treating a patient that has a thyroid carcinoma which has metastasized to the lungs, we will treat with chemotherapy (ex. Palladia) indefinitely. Indefinitely means for as long as chemotherapy helps to keep the disease at least stable, provided the patient tolerates chemotherapy well (feels good on it and doesn't have any concerning blood work changes).
If chemotherapy shrinks the thyroid tumor and resolves some of the lung nodules why don't we stop it? Cancer cells will continue to reproduce if nothing is working to kill them. If we stop chemotherapy, cancer will progress.
I hope this article helped to answer some of your questions about chemotherapy. Next week we'll dive into another chemotherapy topic!
Have questions about this article? Reach out!
Dr. Lori Cesario
Board Certified Veterinary Oncologist