April 21, 2005 Editorial: The Dysfunctionality of Clinical Oncology with Regard to Cancer

     In the pre-chemotherapy era of the 1960s, the median survival of patients with metastatic breast cancer was a little less
     than two years. Since then, the greatest cancer centers in the world have performed hundreds of prospective,
     randomized clinical trials, involving tens of thousands of patients, in an attempt to identify the best treatment to give to the
     average patient, to improve treatment outcome.  The results of these trials have been summarized by Dr. Lawrence
     Shulman, of Harvard's Dana Farber Cancer Center (click here , reference given here). In short, there has been not a hint
     of progress, with median survivals remaining exactly the same, just under two years.

     As Shulman points out, the implications of this are staggering.  Some individual patients are clearly and unambiguously
     helped by chemotherapy.  All breast cancer oncologists have seen individual patients who had dramatic and complete
     regressions of cancer and who enjoyed long survivals. The inescapable, mathematically undeniable conclusion is clear.
     Chemotherapy of metastatic breast cancer is a zero sum game.  For every month a life has been prolonged by
     chemotherapy, there is another month a life has been shortened by chemotherapy. The most likely mechanisms for this
     life shortening are toxicities of the drugs on the patient's body (such as immunosuppression and organ damage) and the
     mutagenic effects of chemotherapy on the genetically-unstable tumor, driving the tumor into a state of more aggressive
     behavior.  The point is that it is not merely a case of either being helped by chemotherapy or not being helped by
     chemotherapy.  Rather, it is a case of being helped by chemotherapy versus being killed by chemotherapy.  Not giving
     toxic drugs which won't work is not abandoning the patient to the disease, it is following the number one rule of
     medicine, which is "first do no harm."

     With these realities, which were clear as far back as the 1980s, it would seem that clinical oncology investigators would
     have abandoned the strategy of performing prospective, randomized trials to identify the best treatment to give to all
     patients, and instead would have devoted most efforts to finding ways to best match individual treatments to individual
     patients.  It is astonishing that this was not done.

     In November of 1999, I was, to my knowledge, the first person to call attention to the fact that clinical oncologists in
     private practice were deriving most of their income by running a retail pharmacy concession, in testimony I gave to the
     Medicare Executive Committee. Subsequently, the New York Times ran an expose, and Public Interest Watch
     essentially accused the American Society of Clinical Oncology of racketeering, in its attempts to prevent reform of the
     more egregiously abusive elements of this system (NYT and PIW articles both cited, referenced, and discussed
     elsewhere on this website).  Basically, I charged that clinical oncologists shop around for the best deals on infusion (i.v.)
     chemotherapy drugs and prescribe chemotherapy, in part, on the basis of which treatments provide them with the
     greatest profit margins.

     We now have proof that my charges were absolutely correct.  Neil Love, MD reports a survey of (1) breast cancer
     oncologists based in academic medical centers and (2) community based, private practice oncologists.  The former
     oncologists do not derive personal profit from the administration of infusion (i.v.) chemotherapy, the latter oncologists do
     derive personal profit from infusion (i.v.) chemotherapy, while deriving no profit from prescribing oral-dosed
     chemotherapy. The results of the survey could not have been more clear-cut.  For first line chemotherapy of metastatic
     breast cancer, 84-88% of the academic center-based oncologists prescribed an oral dose drug (capecitabine), while
     only 13% perscribed infusion (i.v.) drugs, and none of them prescribed the expensive, highly remunerative drug
     docetaxel.  In contrast, among the community-based oncologists, only 18% prescribed the oral dose drug
     (capecitabine), while 75% prescribed infusion (i.v.) drugs, and 29% prescribed the expensive, highly remunerative drug
     docetaxel (click here to see a graph of these data, and click here for a link to the full text of the study [see figure 37,
     volume 2, issue 1, 2005]).  The existence of this profit motive in drug selection has been one of the major factors
     working against the individualization of cancer chemotherapy based on testing the cancer biology.

     The above is not to imply that the academic oncologists are without their fair share of collective guilt. They were
     misguided in not recognizing that they were trying to fit square pegs (one size fits all treatments) into round holes
     (notoriously heterogeneous diseases).  They devoted 100% of their clinical trials resources into trying to identify the best
     treatment for the average patient, in the face of conclusive evidence that this approach was both theoretically nonsensical
     and practically non-productive.  Martin Apple (of the U of Cal San Franciso) sagely noted that "any experiment which
     has failed 1000 times should be viewed with suspicion."  But the corollary is that such unsuccessful experiments will
     never be viewed as such by the thousands of people whose careers are supported by these experiments.

     Here's an example of what passes for a successful experiment in clinical oncology.  Henderson, et al, entered 3,100
     breast cancer patients in a prospective, randomized study to compare cyclophosphamide/doxorubicin alone versus
     cyclophosphamide/doxorubicin plus Taxol (in the adjuvant, pre-metastatic setting).  The results are shown on this graph.
     These results were microscopically positive, at best, and cannot begin to justify the enormous financial and human
     resources expended (while making no effort at all to test and improve methods to individualize treatment).  But these
     results changed the face of the adjuvant chemotherapy of breast cancer.  Thereafter, A/C -> Taxol became standard of
     care.  Taxol recently went off patent.  Now the thrust is to identify on-patent therapy which is microscopically "better," in
     ever more square peg in round hole, clinical trials of one size fits all treatment. Already, the community-based oncologists
     are migrating to A/C -> docetaxel (expensive/remunerative, see Figure 21 in the above-quoted Neil Love study); so
     what was the purpose of that 3,100 patient prospective, randomized Henderson study?

     Buyer (i.e. cancer patient) beware.

     © Larry Weisenthal
     April 21, 2005