There’s a specific routine we follow for each pet arriving for a chemotherapy appointment. Owners arrive and are greeted by a technician, who will ask several questions about how their pet is doing and if any complications from a previous treatment arose.
If all is “status quo,” the patient will be taken to our treatment area, where their vital parameters (temperature, heart rate, respiratory rate, and body weight) will be recorded and the required blood samples will be drawn and run in our laboratory.
I then perform a full physical exam and make sure there are no contraindications to treatment (i.e., health related reasons to withhold treatment).
The oncology technician will retrieve the lab results, examining the printout for any sign that the blood machines are having a meltdown, and if necessary, make blood smears for me to interpret in conjunction with the automated results.
I review the results, then write out the prescription for the chemotherapy drug, including all associated calculations, determining the amount of drug in both milligrams and milliliters where applicable, and reiterating the route of administration (e.g., intravenous, subcutaneous, orally). Every calculation is then double checked by the technician responsible for administering the dosage.
The patient’s body weight, drug, dosage, and amount, as well as results of their lab-work, are manually entered on their “chemotherapy flowsheet,” a tangible record of all prior treatments.
Current dosages are back-checked to that patient’s previous dosages, where applicable. For example, we cross reference their current weight to be sure it is within their previous weights, that it was recorded in the correct units (kilograms versus pounds), and that the dose of chemotherapy is similar to what it was at a previous visit.
This painstaking attention to detail may seem ridiculously tedious. Why is the process of administering a medication so involved—especially when that patient has received the same drug numerous times before? What is the point behind the orderly procession of events we prescribe?
The answer lies in what is known as the narrow therapeutic index of chemotherapy drugs.
Therapeutic index refers to a comparison of the amount of a drug necessary to cause a beneficial effect and the amount causing toxicity.
Paracelsus, a 16th century philosopher, stated, “All things are poison and nothing is without poison; only the dose makes a thing not a poison.” This is frequently paraphrased to, "the dose makes the poison" (Latin: sola dosis facit venenum), an excellent summary of the basis of therapeutic index.
Every prescription medication has a therapeutic index. A dose below the lowest margin of this index will result in a lack of effectiveness. A dose above the highest margin can lead to side effects. In the most extreme cases, the side effects can equal death. Dosages within the therapeutic index will be effective for treating the condition in question, but will remain non-toxic for the patient’s healthy cells.
Some prescriptions have a wide therapeutic index, and veterinarians have a good deal of “wiggle room” in what can be dispensed based on a given patient’s size.
For example, the same exact dosage of an antibiotic can be equally therapeutic for a 30lb dog as for a 50lb dog. Similarly, a 50lb dog can be prescribed 2-3 tablets of a particular pain medication to be given every 8-12 hours. The wide therapeutic index of those drugs allows for such variations.
Chemotherapy drugs, on the other hand, have little to no safety margin and a very narrow therapeutic index. This means the dosage of a chemotherapy drug necessary to cause an anti-cancer effect is very similar to that which causes adverse effects.
Therefore a slight error in calculation leading to even a minuscule overdose of drug can lead to catastrophic effects for that patient. In those cases, the patient’s healthy tissues will be exposed to levels of drug that can be at best moderately damaging or permanently affected, and at worst cause a fatal reaction.
We might be able to cure more cancers in pets if we could give them higher dosages of chemotherapy, but we would also bring those animals to the brink of death before any potential success. This is neither an ethically or financially feasible option in veterinary medicine. We also would have a much higher death rate from treatment, losing large numbers of patients to complications from treatment rather than disease.
I’d be remiss if I didn’t acknowledge that at least part of my anxiety about dosing chemotherapy arises from my Type A personality. I’m known for calculating and re-calculating doses several times before giving a thumbs up on the prescription (and even continuing to recheck calculations as the drug is being given). My paranoia stems from knowing all the things that can go wrong when the therapeutic index is breached. However, it’s certainly fueled by a tiny bit of compulsion as well, as I tend to be more obsessive about such details than my colleagues.
With proper and meticulous attention to detail, I’m ensuring that the therapeutic index of chemotherapy drugs I prescribe isn’t breached and errors are avoided.
Although it’s certainly monotonous to perform so many extra steps for every appointment, the process is integral to guaranteeing my patients are treated with the same standard of care I would expect for myself.
The dose certainly makes the poison, but there’s no poisoning allowed on my watch.
Dr. Joanne Intile