Dr. Robert A. Nagourney, MD
Is The Role Of The Oncologist To Add Drugs or Subtract Drugs?
When I was a medical oncology fellow at Georgetown University, I worked with capable infectious disease experts.
As cancer chemotherapy causes immune suppression, cancer patients often meaningfully benefit from the early input of infectious disease specialists.
Modern medicine’s access to highly active antibiotics made it possible to broadly cover patients with effective combinations. Indeed, when patients presented with infections of unknown origin, the coverage used was so expansive that we called it “Umbrellacillin,” conjuring images of an umbrella covering every imaginable pathogen.
Over time I came to realize that the role of the infectious disease expert was not to add antibiotics but to subtract them. They used their expertise to hone drug combinations to a rapier point. As antibiotics can have deleterious effects on the gastrointestinal tract, clinical studies from Sloan Kettering and other institutions have shown that continuous antibiotic coverage can adversely affect survival in diseases like leukemia.
This is not to say that antibiotics are bad but instead to say that the indiscriminate use of multi-agent antibiotic regimens may be bad for some patients.
We are now witness to a related phenomenon in cancer medicine, reminiscent of antibiotics.
Beginning with multidrug combinations in high-grade lymphoma culminating in the absurdly complex ProMACE-CytaBOM, the “more is better” field collapsed when the most basic treatment from the 1970’s known as CHOP beat out all the other drug combinations from the 1980s and 1990s and provided better survival with less toxicity.
Now oncologists who treat colon and pancreatic cancer are falling prey to the same thinking. FOLFIRI and FOLFOX have given way to FOLFOXIRI in colon cancer, while in pancreatic cancer they’re adding Cisplatin to Abraxane plus Gemcitabine, leading to some improvements in response but at the cost of demonstrably greater toxicity.
Like our colleagues in infectious disease, medical oncologists must learn to subtract drugs that do not contribute to response. Drug inclusion should be based upon a clear combinatorial rationale. To achieve this we must craft combinations based on each patient’s tumor sensitivity and where possible synergy for the drugs selected.
We are educated by our infectious disease colleagues, who have used combination therapies for decades, and who know that in medicine more is not necessarily better. It is critical that oncologists not add drugs indiscriminately. Oncologists must avoid the temptation to add drugs because they can and learn to add drugs because they work.