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Hope or hoax? How to evaluate veterinary cancer therapies
Use these five questions to determine whether certain oncology therapies might benefit your patients on their path toward better health.
“Hey, doc, I was doing some research online, and I found this new treatment. Do you think it'll help with Buddy's cancer?”
Small animal veterinarians often hear some variation of this question from pet owners. Most of the time, the treatment in question is one that the veterinarian has never encountered and knows little about. With precious little time to undertake exhaustive research into every therapy marketed for pet cancer, practicing vets might (understandably) feel a sense of exasperation trying to answer these questions accurately and fairly. However, by asking themselves a few simple questions first, busy practitioners can make efficient use of their time to determine whether a therapy is likely to be beneficial for their patients.
Question 1: Is the therapy described in peer-reviewed scientific literature?
The first acid test for evaluating an unfamiliar cancer therapy's potential efficacy is whether it's referenced in PubMed, CAB Abstracts or another online database of reputable scientific literature. If the therapy or its active ingredient are not indexed in one of these databases, it's less likely to be effective.
Question 2: Have results been published of clinical trials using the therapy in animals with a naturally occurring disease?
Therapies that have only shown anti-cancer efficacy in the in vitro setting, rather than in clinical trials in the target patient population, are unlikely to be effective. Frequently, therapies that show promising anti-cancer activity in vitro (such as in cell culture) fail to show similar promise when tested in the target species (such as humans or companion animals). There are several reasons for this, including differences in tumor biology or differences in drug pharmacokinetics in experimental vs. real world settings. And speaking of pharmacokinetics …
Question 3: What is known about the pharmacokinetics and pharmacodynamics of the drug in the target animal species?
Pharmacokinetics?! Pharmacodynamics?! Really?! Yes, these arcane subjects that probably tormented you in veterinary school actually do matter when critically evaluating anti-cancer drugs. Drugs that kill cancer cells perfectly well in a petri dish may only do so at concentrations that cannot be achieved in blood plasma after administering the drug to an animal, or can only be achieved by administering doses that are excessively toxic. Drugs are less likely to be efficacious if published research has not documented a specific pharmacodynamic effect (such as tumor regression) in the context of pharmacokinetic data showing that the effect is possible following the administration of tolerable drug dosages.
Question 4: If the therapy claims to benefit small animal patients with cancer, how was benefit measured?
Fundamentally, there are only two ways a therapy can benefit patients with cancer: 1) The therapy causes measurable cancers of a defined histologic type to undergo significant reduction in size in some proportion of animals with that cancer and 2) a group of animals treated with the therapy lives significantly longer or experiences a significantly longer time to cancer progression than a group of contemporaneously treated animals that did not receive the therapy (i.e. a control group of animals).
The first of these is easy to demonstrate in clinical trials involving relatively small numbers of animals. The second, on the other hand, is difficult to demonstrate, as the clinical trials required to do so with adequate statistical power involve large numbers of animals, are time-consuming and, consequently, are expensive to conduct. As a result, few such trials related to veterinary cancer therapies are ever undertaken.
However, the importance of a representative control group in cancer trials where patient survival is the benchmark for efficacy cannot be overstated. For example, cancer therapies given after surgical tumor removal to prevent tumor recurrence may be deemed beneficial when patients receiving the therapy experience live longer or appear to be cured. Without results from a contemporaneous control group treated with surgery alone, however, it's impossible to tell if the “cures” resulted from the new therapy or simply from surgical tumor removal itself.
Similarly, the efficacy of new cancer therapies may be reported in comparison to a historical control group of animals in a previous trial. Historical control groups are rarely, if ever, faithful surrogates for contemporaneous control groups. In fact, studies have shown that the results of clinical trials incorporating historical control groups tend to be biased in favor of new therapies. Therapies that purport to improve survival relative to historically treated animals therefore should be regarded with some circumspection.
Question 5: What are the side effects or possible complications associated with the therapy?
All medical interventions cause side effects. While the risk of side effects can vary from quite low to quite high for a given treatment, all treatments will produce some side effects with a defined frequency. Because of this, veterinarians should be wary of cancer therapies claiming to produce no side effects.
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Rather, veterinarians should pay closer attention to therapies claiming to produce “acceptable” or “tolerable” side effects. Effective cancer drugs for small animals will produce side effects, but these can often be mitigated by dosage modification or administration of other treatments at the same time. A therapy producing “no side effects,” on the other hand, should be suspected of simply being biologically inert.
By seeking the answers to these five simple questions, veterinarians can screen new cancer therapies for promising efficacy quickly and efficiently. Therapies that seem favorable after asking these questions may warrant additional research, while those seeming dubious probably do not. It's important to realize that these questions should be asked not only of therapies identified on the internet by pet owners, but also of those produced and marketed by major pharmaceutical companies or under clinical evaluation at academic teaching hospitals. No matter how trusted the source of a new drug might be, it's still deserving of your careful scrutiny when judging whether the drug is a good option for your patient.
Michael O. Childress, DVM, MS, DACVIM (Oncology) is associate professor of comparative oncology at Purdue College of Veterinary Medicine.