The use of metronomic chemotherapy in dogs
Over the last several years, human and veterinary researchers have been interested in therapies that target angiogenesis. If we can prevent blood-vessel proliferation by the tumor, we may be able to prevent progression of many cancers.
This type of therapy, often referred to as low-dose continuous chemotherapy (LDC), may have significant advantages over standard, high-dose therapy, in that fewer severe side effects may be seen, in addition to improved anti-tumor effects.
Also, we may be able to administer drugs over a longer period, because there is minimal need to allow the body to recover. Eliminating the need for breaks between cycles of maximally tolerated dosage (MTD) chemotherapy may lead to improved tumor-cell kill, as the endothelial lining does not have a chance to regenerate with the LDC approach.Chemotherapy drugs work, not by specifically targeting tumor cells, but by interfering with cell division via inhibition of microtubule formation, DNA replication, etc. Thus, these drugs also will damage the normally rapidly dividing population of cells as well, such as the bone-marrow progenitor cells, intestinal mucosal-lining cells and vascular endothelial cells. This often results in a narrowed therapeutic index when conventional MTD is used.
Furthermore, based on the fact that quality of life is an absolute requirement in our animal patients, as veterinary oncologists our MTD is less than that in human patients. Therefore, we struggle to cure most of our patients because it is inappropriate for us to be as aggressive in our therapies.
High-dose chemotherapy, with the required breaks in treatment, not only allows for resolution of the drug-induced bone-marrow suppression, but seems to provide time for the endothelial cells to regenerate.
Using LDC provides continuous suppression of the repair process of the blood vessel, thus robbing tumor cells of their nutritional support. Interestingly, even if a tumor cell is resistant to a particular chemotherapy agent at the MTD, the vascular endothelial cells still are sensitive when LDC is employed.
In a paper by Lana, et al. (J Vet Intern Med 2007; 21:764-769), dogs with Stage II hemangiosarcoma were treated with LDC and survival times were compared to dogs treated with conventional MTD chemotherapy. The LDC was well tolerated over a period of six months. The median overall survival time and median disease-free interval were 178 days. For dogs treated with doxorubicin chemotherapy, the overall survival time and disease-free interval were 133 and 126 days, respectively.
While this was a relatively small study (nine dogs were treated with LDC), this paper suggests that LDC may be an effective alternative to MTD chemotherapy in dogs with hemangiosarcoma.
Dr. Rosenberg, a diplomate of the ACVIM in oncology, received her veterinary degree from UC-Davis in 1987. She completed her internship and residency in medical oncology at the Animal Medical Center. Dr. Rosenberg was awarded the David S. Brody Award for Clinical Excellence in 1990 for her work in lymphoma and hypercalcemia. In 1992, she founded the Veterinary Cancer Group. Having built two comprehensive cancer centers in Southern California, Dr. Rosenberg leads the largest private animal-oncology practice in the nation.