Dr. Robert A. Nagourney, MD
Let's Talk About “CHEMOTHERAPY”
Raymond Carver’s 1981 collection of short stories, “What We Talk About When We Talk About Love” was featured in the 2014 movie, Birdman. I am reminded of this catchy title for a short story but in a different context.
What doctors talk about when they talk about chemotherapy. For oncologists today chemotherapies are protocols. They are standardized treatment regimens that have been established in clinical trials. The drugs themselves have names, sometimes referred to by their generic names more often by their commercial names.
When doctors talk about chemotherapy, they do not see mechanisms, they do not see structures, they do not see synergy, drug interaction, antagonism, or other aspects of pharmacology so critical to the selection of active treatments. Instead, they see published literature with marginal statistical significance and little impact on actual survival.
To address the shortcomings of contemporary clinical-trial-driven drug selection for individual patients, we decided to “cut to the chase” and use each patient’s own tissue to study drug activity.
What does that mean?
It means that every cancer patient has their own unique profile.
A patient's tumor is either sensitive to a drug or not.
It is either synergistic with a second drug or not.
It is either sensitive to a third drug or not.
These sorts of questions are part of a hierarchical clustering that ultimately leads you to the right answer. Like Boolean logic that eliminates wrong answers until it finds the right one, this leads to the best treatment for each patient.
It is not to say there is a perfect treatment for every patient - certainly not. There are some patients for whom available treatments, even the newest treatments won’t work. Cancer is extremely complex and the biological systems that drive the survival of cancer cells are poorly understood even by the most sophisticated scientists.
What we do see are unexpected degrees of activity for drugs. A patient with a P53 mutation might be expected to be drug-resistant, yet one of my most successful outcomes was a young man with the P53-mutation-driven, Li-Fraumeni syndrome, who had a near-perfect response to assay-selected platinum-based chemotherapy.
It was not so important why he responded but instead that he responded. We need to return to the practical utility of chemotherapy drugs that work. Period!
Our laboratory uses each patient’s tissue removed from the body under sterile conditions to examine drugs, combinations, targeted agents, metabolic inhibitors, and novel combinations.
Does it work? Yes, very well, providing improved response and survival. Contrary to conventional chemotherapy where one obtains a doctor’s opinion on the best treatment, we provide objective, quantifiable data. Opinions are fine when writing a movie review or an OpEd, but for life and death matters like cancer, patients need more.
Patients should avail themselves of tissue culture technologies that utilize fresh tumor explants to identify the most active, least toxic, treatments. To do otherwise is to guess and for most cancer patients today guessing doesn’t seem to be working very well.