Managing Chemotherapy Side Effects
Typical Chemotherapy Doses
Maximum tolerated dose chemotherapy involves bolus treatments with the highest possible dose of conventional chemotherapy drugs (intravenous or oral). The treatments are given at specific intervals of time and the time between treatments allows normal tissue to recover. The limiting factor in chemotherapy dosing is finding the balance between an effective dose and unacceptable side effects. Mild chemotherapy side effects occur in 10-20% of pets, and approximately 5% of patients will experience severe side effects that require admission to the hospital for management. There is a <1% chance of death when treating patients with chemotherapy appropriately. With over 15 years of experience treating dogs and cats, Dr. Binstock can help you tailor chemotherapy doses for your patients.
Receptor tyrosine kinases (RTKs) are tyrosine kinases that reside on the cell surface that are activated through binding growth factors. Receptor tyrosine kinases play a critical rose in the signaling pathways the control normal cellular processes such as proliferation, migration, metabolism and differentiation. Mutations of RTKs can occur during the development and progression of cancer, and they are targets for therapeutic intervention. Whereas traditional chemotherapy kills all rapidly dividing cells, tyrosine kinase inhibitors (TKIs) are targeted therapies that inhibit specific receptors on the surface of cancer cells and nearby blood vessels. TKIs inhibit tumor growth through direct effects on cancer cells as well as via anti-angiogenic mechanisms. Palladia (toceranib phosphate) is the only FDA approved veterinary TKI. It is licensed for use in the treatment of canine mast cell tumors, but is used off label to treat a variety of other in cancers in dogs and cats. Palladia is administered in tablet form three times a week or every other day. Palladia is well tolerated in general but can cause gastrointestinal upset, neutropenia, muscle pain, protein losing nephropathy, and other side effects. If a side effect occurs, it will usually resolve when 1-2 doses are skipped and symptomatic therapy is instituted. While on Palladia the patient should be monitored monthly via lab work and a physical examination.
Small Molecule Tyrosine
Metronomic chemotherapy involves the use of low-dose daily medications including a chemotherapy drug such as cyclophosphamide or chlorambucil and an oral non-steroidal anti-inflammatory such as carprofen or piroxicam. Metronomic chemotherapy alters the tumor microenvironment. Tumor cell endothelium is more proliferative than endothelium within normal tissues, making it a potential target for chemotherapy drugs. Targeting the tumor cell endothelium with metronomic chemotherapy implies a shift in the target that is being treated. In addition to its anti-angiogenic effects, metronomic administration of chemotherapy alters the dynamics of the immune system to favor innate tumor killing. Regulatory T cells (Tregs) inhibit T and natural killer cells; metronomic cyclophosphamide has been shown to suppress Tregs which allows for stimulation of the immune system.
Side effects associated with low-dose chemotherapy are minimal but most often involve gastrointestinal upset and immunosuppression with chronic use. Some dogs will experience sterile hemorrhagic cystitis with cyclophosphamide. This complication can resolve in a few weeks but in some cases can be prolonged and the treatment options are limited. Therefore, I typically recommend drug chlorambucil instead since it does not have this side effect. Lab work and an exam are recommended approximately every 8 weeks.
This type of care focuses on providing pets with relief from symptoms of their cancer. It typically involves management of pain, diet adjustments, appetite stimulants, etc. In some cases, radiation therapy or specific medical therapies may be recommended to improve comfort. The goal is to maximize quality of life for each individual pet and support the owner as much as possible. The transition to hospice care allows us to provide your patients the most dignified, painless death possible.