There are three forms of clinical trials for chemotherapy drugs. The first is a Phase 1 trial, or dose-escalation study. Phase 1 studies are designed to determine 1) What is the optimal dosage of a new chemotherapy drug for the particular species in question? and 2) What are some of the side effects that could occur from the new drug?
Patients with various tumor types are enrolled in Phase 1 trials because the primary goal is not to determine efficacy of the treatment, but rather what dose of the drug can safely be administered. Pets enrolled in such trials often have advanced stage cancers with a very poor prognosis, no other reasonable treatment option, and we are looking to learn something from their condition and how their bodies may react to a drug in question.
During a Phase 1 trial, patients are enrolled into what are known as cohort groups. There are usually three patients in each cohort. Each cohort group will receive the drug in question at a particular pre-determined dosage. The "endpoints" for toxicity for each cohort group will be pre-determined and will be quantified by very specific criteria. If none of the patients in that cohort experience any side effects, the dose of the drug will be increased by a specific amount, and another three dogs in a new cohort will be enrolled.
If one patient experiences too severe of a toxic reaction, the cohort will be expanded to enroll another three patients. If two patients experience too severe of a reaction, this will be considered a "maxillary tolerated dose" and the dose will be lowered to the previous cohort's dose (or if this happens at the starting dose, a lower dose will be used). Sometimes when owners hear the goal of a Phase 1 study, they are too nervous to enroll their own pets because of fears for unknown side effects.
Once the Phase 1 study is complete and we know the safe dose we can administer, the drug is entered into a Phase 2 trial, where we learn about the efficacy of the drug. Patients enrolled in a Phase 2 trial must have at least one measurable tumor because we want to know if the drug is useful for making the tumor shrink. This will automatically eliminate pets whose tumor was removed surgically, or previously treated and eradicated, but the risk of metastatic disease is very high. For patients in a Phase 2 trial, we also have to know the exact nature of the tumor. This will eliminate pets we "suspect" of having cancer, but do not have a definitive diagnosis.
For a Phase 2 trial, we must determine ahead of time what a "meaningful response rate" is, as this will determine the number of patients we need to enroll in a trial in order to provide statistically sound results. Unlike media portrayal, a clinician cannot simply decide, "Hey, I have this drug I think will work well against cancer. Who wants to sign up?" This is precisely where most veterinary studies fail, and results are reported as purely numerical values, without statistics to back them up.
Drugs that show promise in Phase 2 trials are then enrolled in Phase 3 trials. Here, the new treatment is compared to what is considered the "standard of care" treatment for that particular tumor type, or a placebo if no standard of care is available.
Ideally, patients are 1) randomly assigned to groups in order to avoid bias in selection, and 2) blinded as to the treatment they are receiving, meaning there is no way the patient, owner, or clinician would know what drug (or placebo) the patient was receiving. Obviously, there are ethical considerations for Phase 3 trials and as such, placebos are uncommon in veterinary studies. Phase 3 trials are also very difficult to implement as they typically require the enrollment of large numbers of patients into each treatment group in order to prove a statistically significant difference.
Each level of testing requires planning, tedious data recording, time, expertise, enrollment of large numbers of patients, and typically some form of financing. It's never as simple as saying, "I have this patient with a very rare cancer that may occur in 1 out of 100,000 dogs. Who wants to help me study how to treat it?"
Even the "best" veterinary cancer studies enroll only 20-50 patients over a period of 1-2 years (compared to human oncology studies where thousands of patients are enrolled over a decade or more). It's hard to draw adequate conclusions from our studies, and it's even more difficult to translate the limitations to owners.
I would love to be able to offer new and exciting options for owners, and I appreciate when they are open to my ideas or consider more "experimental" treatments with the hope of helping other animals in the future. But there are some major limitations to doing this effectively, especially in a busy private practice setting.
This all started me thinking, it's about time veterinary specialists stepped up to their responsibilities to advance our fields and figured out how to effectively collaborate rather than keeping it all behind our own exam room doors.
I feel it would be the most effective way we can start to successfully attack cancer rather than chip away at it with ineffective protocols that are decades old. If owners are willing to give it a try, shouldn't we figure out how to make it happen?
Dr. Joanne Intile