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www.pbgv.org

Summer 2015   

I Saber Tails

Next Saber Tails deadline — July 15

Most of us have had a loved one stricken by cancer and,
thus, we are familiar with the conventional cancer
chemotherapeutic approach. Traditionally, a cancer patient
is treated with a high dose of a drug, or drug combination,
that is more toxic to rapidly dividing cancer cells than to
normal tissues. The patient typically suffers side effects such
as nausea, hair loss and fewer red blood cells. The treatment
is followed by a break to allow drug-sensitive normal 
tissues to recover. Then the treatment is repeated. This 
conventional chemotherapy has led to improved survival
for many cancer patients, but it often fails.

Dr. Barbara Biller is a veterinary oncologist at the Flint

Animal Cancer Center, affiliated with Colorado State 
University. Her research, funded in part by the AKC Canine
Health Foundation, is testing a new approach to cancer
chemotherapy, called metronomic chemotherapy. A
metronome is a device that produces a regular tick, tick, 
tick that musicians use to keep a steady tempo. Metronomic
chemotherapy is the daily administration of a low dose of
the same toxic drugs as conventional chemotherapy. This
low dose doesn’t kill the tumor cells, but there is evidence it
does prevent the growth of blood vessels into the tumor.
Starved of nutrients, the tumor dies. The metronomic dose
also appears to “wake up” the immune system, leading to 
an antitumor immune response.

Metronomic chemotherapy has been tested in several

human clinical trials with patients who had advanced 
cancer that had failed to respond to conventional
chemotherapy. Dr. Biller reports that, despite promising 
results, metronomic chemotherapy is still considered 
investigational and is not offered as a first-line therapy.

Dr. Biller cites nine published clinical trials of 

metronomic chemotherapy in dogs and cats. The treatment
is easy to administer, reasonably priced and well tolerated.
There is early evidence of overall clinical benefit. Dr. Biller
states, “Although metronomic chemotherapy is an attractive
treatment choice, it is still considered an experimental 
approach with the potential for toxicity. When available,
conventional therapies should first be offered before turning
to a metronomic protocol. Because stable disease is generally
the goal of therapy, it is also important to consider the 
overall condition of the patient; living with stable disease
should be expected to result in an acceptable quality of life.
When used appropriately, there is much potential for 
metronomic chemotherapy to improve, not just maintain,
quality of life for companion animals with cancer, especially
as additional studies answer important questions regarding
indications, drug dosages and patient monitoring.”

For more information on Dr. Biller’s research, see the 

following: www.akcchf.org/news-events/library/
articles/metronomic-chemotherapy.html.

Seizures  continued from page 52    for treatment of the canine
disease, as there has been for human status epilepticus. Dr.
Patterson states, “There does seem, however, to be fairly 
similar recommendations from a number of sources that 
can be generally summarized as:

“1. First-line therapy should be with a benzodiazepine,

which most often is intravenous diazepam, but can be 
by other routes and/or with midazolam, or lorazepam. 
There have not been any published studies comparing 
benzodiazepines to each other in dogs or cats as there has
been for people. Shortly after the benzodiazepine, there
should be intravenous loading or mini loading doses of 
intravenous phenobarbital or intravenous [levetiracetam] 
to start chronic therapy, for when the short-acting
benzodiazepines wear off.

“2. In second-line therapy for continuing seizure activity,

intravenous phenobarbital or intravenous LEV or a [constant
rate infusion] of diazepam or midazolam should be given.
The author has found that two or more of these second-line
therapies can potentially be given to the same patient.

“3. Third-line therapy of [refractory status epilepticus] to

induce general anesthesia can be with intravenous propofol
or pentobarbital. In some instances, IV ketamine or inhalant
anesthesia has been administered.”

Research over the past decade has tested new approaches,

which Dr. Patterson hopes will lead to paradigm shifts in
treatment for seizures. These include neurosteroids, gene
therapy, use of molecules that alter gene expression, and
new biochemical targets. Dr. Patterson concludes, “Status
epilepticus in companion animals is an emergency and
should be quickly treated by recommended first-line 
(emergent) therapy with benzodiazepines followed by 
loading doses of chronic therapy drugs, and then second-
line, and third-line (refractory) therapy when needed. 
Cluster seizures can evolve into status epilepticus, and 
therefore at-home treatment with per rectum or intranasal
benzodiazepines and longer-acting oral antiepileptic drugs
for dogs is often recommended, and if not effective, then
hospitalization for observation and treatment as for status
epilepticus are recommended.”

Metronomic Chemotherapy in Veterinary Patients with Cancer.
Rethinking the Targets and Strategies of Chemotherapy.

Barbara Biller, DVM, PhD
Vet Clin Small Anim 44(2014) 817-829