There has been a trend in medical oncology to add therapies, layer upon layer, until every patient receives every drug every time. In colon cancer, 5-FU was first combined with leucovorin. Then came Oxaliplatin (FOLFOX) and Irinotecan (FOLFIRI) and more recently Bevacizumab (Avastin) and Cetuximab (Erbitux). Now FOLFOXIRI+Avastin, a regimen that combines virtually every drug known to be active in colorectal cancer, is becoming the preferred 1st-line treatment for this disease.
Lung cancer has followed the same path. Surgery and radiation gave way to combinations with chemotherapy, before, after or during. Responding patients now receive maintenance therapy with Alimta +/- Avastin for 4 cycles. Second and even 3rd line therapies now have patients with NSCLC (Non Small Cell Lung Cancer) being exposed to virtually every known drug.
The problem is that while some patients may require complex treatments, there are many who could do as well or better with simpler less toxic, less costly therapies. The original lung cancer trial that added Avastin to standard Carboplatin & Taxol improved the median survival from 10.3 months to 12.3 months, a 2 month improvement. Despite achieving statistical significance, many complicated and potentially toxic regimens do not work better for everyone, yet they demonstrably increase the cost and toxicity of treatment.
The Infectious Disease (ID) literature offers insight as the ultimate role of an infectious disease specialist is not to add antibiotics, but to eliminate them. Their expertise enables them to narrow treatments to only those that are effective. Every internist confronting an infected patient has the capacity to add antibiotic coverage for every known organism, in fact they often do. It’s the role of the ID consultant to narrow the field to just the needed drugs. Thus, the role of medical oncologists in NSCLC may be to give fewer not more drugs.
Case of 74-yr-old Stage IV NSCLC Patient
This is exemplified by a very pleasant 74-year-old woman who came to me 2 years ago with metastatic NSCLC. Initial empiric therapy provided a response, but by one year she had progressed. I recommended a biopsy for the EVA/PCD functional profile. The results were highly instructive. While many Stage IV NSCLC patients would receive complicated combinations, this patient revealed exquisite sensitivity to single agent Taxol.
With symptomatic progression I began Taxol. At the beginning of treatment the CEA was 1294 (normal 0-5). The treatment was well tolerated, but resulted in alopecia (hair loss) and mild neuropathy (weakness, numbness or pain in hands or feet). Now eight months later the CEA has fallen to 7.1 and, with the exception of the alopecia, she is the picture of health.
The lesson is that patients should receive the right drug, not every drug in the compendium. While complex combinations enable physicians to gain small advantages in response rate, they come at enormous cost, both in toxicity and expense. This patient has suffered little toxicity because she received exactly the right treatment.
Careful selection of therapies is the future of cancer medicine. Functional analyses, that have been the subject of a recent editorial in Nature, are not a future possibility, they are available today.
As always, I welcome your questions and comments.