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  • Dr. Robert A. Nagourney, MD

SEVEN WITH ONE BLOW: OVERCOMING THE ODDS IN CANCER

Updated: Oct 25

Of all medical specialties, oncology is among the most demanding. Our patients confront

life-threatening diseases with treatment options that are toxic and often ineffective.

Cancers arise in and affect the function of every organ of the body. The advanced state of

many patients’ cancers makes the practice of oncology emotionally distressing as

oncologists are often the bearers of bad news. Indeed, there’s a well-described

phenomenon of oncologist burn-out describing those practitioners who find their chosen

specialty too distressing and decide to retire.


Those who have read my blogs know that I apply the EVA/PCD laboratory method to

select treatments and combinations. This grants me a higher level of confidence that a

chosen treatment will provide a response and can allow me to adjust doses predicated on

my foreknowledge of a combination’s likelihood of success.


It is difficult for me to imagine practicing oncology without this tool. As the platform

doubles the expectation of response and improves survival, I apply it for every patient.

My clinical practice has focused increasingly on difficult-to-treat, advanced, and often

refractory patients. I have an interest in pancreatic, triple negative breast cancer and

recurrent diseases for which available therapies are often limited. I see a wide variety of

tumor types and patients of all ages and geographic origins.


With my interest in tumor biology, I view cancers through the lens of cellular changes

rather than individual tumor types. We often use re-purposed drugs taken from one

disease and applied to another, based not on FDA indication, but instead on the degree of

activity in a given individual.


It was the brothers Grimm who authored "Seven-with-one blow," the 19th century German fairytale about a tailor who applied his wits to rise from humble origins to become king

of the land. I was reminded of this tale as I surveyed the outcomes of seven consecutive

patients from a recent clinic.


The first is an 86 year old woman who presented over a year ago with inoperable

pancreatic cancer. A biopsy identified an active but very mild drug combination and she

achieved a rapid remission almost without toxicity. As her 87th birthday approaches, she

continues to do extremely well and enjoys a normal and very active life.


The next is a patient who presented with advanced lymphoma and achieved a complete

remission. His occasional follow ups are now spent catching up on his exploits and

active life style. The next had a BRCA2 positive breast cancer but achieved an excellent response with laboratory selected platinum-based treatment. Now three years later she has returned to

normal life with no evidence of disease.


The next patient is a gentleman who presented with extremely high grade, advanced,

prostate cancer. Predicated on work I had conducted years earlier examining

chemotherapy in prostate cancer, I applied a triple modality therapy of radiation,

hormonal and chemotherapy using an approach I pioneered 20 years ago.


Now, at two years, he remains in an unmaintained complete remission without further therapy.

Next was a woman who presented with a large breast cancer originally diagnosed as

triple negative but who upon second biopsy was found estrogen receptor positive tumor,

which completely changed the choice of drugs. Using that biopsy she responded nicely

and was consolidated with drugs that target both triple negative and ER positive breast

cancer. With no evidence of disease her hard-fought battle has been an unqualified

success.


Another lymphoma patient came to me from Stanford University where he had been

treated by an accomplished investigator. With disease progression he traveled to Los

Angeles and a biopsy revealed striking activity for a mild two-drug combination that I

had previously described (Nagourney, RA Br J of Cancer, 1993). Achieving a complete

remission he is perfectly well now 22 years later.


My seventh patient is of particular importance. With progressive breast cancer and failing

all hormonal interventions, her doctor, at one of the leading cancer centers in Los Angles

recommended oral Capecitabine. This is a reasonable choice and generally well tolerated

but the patient, whose disease was progressing rapidly wanted a higher degree of

certainty and submitted a tissue biopsy for analysis.


The results showed that by adding a second very mild drug to the Capecitabine, the

expectation of response was measurably increased. But when I reported the suggestion,

the patient’s physician outright refused to administer this well-known and widely used

drug doublet, one that I had helped develop years earlier (Brewer, C, et al. Proc. AACR,

2007). The patient opted instead to travel to our office for her care and has had an

excellent response since beginning therapy in December, all with no toxicity whatsoever.


I describe the experiences from a just one clinic, as it is hard for me to imagine treating

patients without the benefit of objective data. With the relatively low response rates, high toxicities and emotional distress associated with ineffective therapy, I too might be considering leaving practice were it not for my laboratory platform; one more victim of oncologic-burnout. Instead, I come to work with a sense of pride and accomplishment.


I don’t mean to suggest that every one of my patients responds or that I cure everyone.

That certainly is not the case. Some of my patients do progress and even those who

respond can relapse. But our results are better and many of our patients carry on normal

lives. This is one of the greatest the rewards of medicine and I feel fortunate to be able to

enjoy that reward, even as I confront cancer, among the most difficult diseases to treat.

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