Does Chemotherapy Work? Yes and No.

A doctor goes through many stages in the course of his or her career. Like Jacques’ famous soliloquy in Shakespeare’s “As you Like It,” the “Seven Ages of Man,” there are similar stages in oncologic practice.

In the beginning, fresh out of fellowship, you are sure that your treatments will have an important impact on every patient’s life. As you mature, you must accept the failures as you cling to your successes. Later still, even some of your best successes become failures. That is, patients who achieve complete remissions and return year after year for follow-up with no evidence of disease, suddenly present with, a pleural effusion, an enlarged liver or a new mass in their breast and the whole process begins again.

I met with just such a patient this week. Indeed when she arrived for an appointment, I only vaguely remembered her name. After all, it had been 13 years since we met. When she reintroduced herself I realized that I had studied her breast cancer and had found a very favorable profile for several chemotherapy drugs. As the patient resided in Orange County, CA, she went on to receive our recommended treatment under the care of one of my close colleagues, achieving an excellent response to neo-adjuvant therapy, followed by surgery, additional adjuvant chemotherapy, and radiation. Her decade long remission reflected the accuracy of the assay drug selection. She was a success story, just not a perfect success story. After all, her large tumor had melted away using the drugs we recommended and her 10 year disease-free interval was a victory for such an aggressive cancer.

A dying leukemia cell

A dying leukemia cell

So what went wrong? Nothing, or more likely, everything. Cancer chemotherapy drugs were designed to do one thing very well, stop cancer cells from dividing. They target DNA synthesis and utilization, damage the double helix or disrupt cell division at the level of mitosis. All of these assaults upon normal cellular physiology target proliferation. Our century long belief that cancer was a disease of cell growth had provided us a wealth of growth-inhibiting drugs. However, in the context of our modern understanding of cancer as a disease of abnormal cell survival (and the need to kill cells outright to achieve remissions), the fact that these drugs worked at all can now be viewed as little more than an accident. Despite chemotherapy’s impact on cell division, it is these drugs unintended capacity to injure cells in ways they cannot easily repair, (resulting in programmed cell death) that correlates with response. Cancer, as a disease, is relatively impervious to growth inhibition, but can in select patients be quite sensitive to lethal injury. While cancer drugs may have been devised as birth control devices, they work, when they do work at all, as bullets.

There is an old joke about aspirin for birth control. It seems that aspirin is an effective contraceptive. When you ask how this simple headache remedy might serve the purpose, the explanation is that an aspirin tablet held firmly between the knees of a young woman can prevent conception. The joke is emblematic of chemotherapy’s effect on cancer as a drug designed for one purpose, but can prove effective through some other unanticipated mechanism.

Chemotherapy does work. It just does not work in a manner reflective of its conceptualization or design. Not surprisingly it does not work very well and rarely provides curative outcomes. Furthermore, its efficacy comes at a high price in toxicity with that toxicity reflecting exactly what the chemotherapy drugs were designed to do; stop cells from growing.  It seems that the hair follicles, bone marrow, immune system, gastrointestinal mucosa and reproductive tissues are all highly proliferative cells in their own right. Not surprisingly, chemotherapy extracts a heavy price on these normal (proliferative) tissues. It is the cancer cells, relatively quiescent throughout much of their lives that escape the harmful effects.

As a medical oncologist in the modern era, I have recognized only too well the shortcomings of conventional cytotoxic drugs. It is for this reason that I use a laboratory platform to select the most effective drugs from among the many badly designed agents. Culling from the herd those few good drugs capable of inducing lethal injury these are the ones that the EVA-PCD assay selects for our patients. Applying this approach, we have doubled responses and prolonged survivals.

Over the past decade we have focused increasingly on the new signal transduction inhibitors and growth factor down regulators. If we can double the response rates and improve survivals using our laboratory assay to select among bad drugs, just imagine what our response rates will be when we apply this approach to good drugs.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

7 Responses to Does Chemotherapy Work? Yes and No.

  1. jIM says:

    Chemo therapy has a very low success rate and no wonder its a deadly poison. An oncologist that administers chemo therapy understands that the end result will be death of the patient. The key to a patients survival is their immune system and chemo therapy rips it to shreds. Doctors are deliberately with holding cancer cures from patients for fear of being destroyed by big-Pharma , the FDA , W.H.O and others. The sickening fact is they have traded humanity for a dollar. Western medicine is barbaric ,shameful and criminal. When a patient is diagnosed there is much information not discussed or given and this is just wrong. The average doctor knows almost nothing about nutrition instead they are taught drugs and drugs will never be the answer to stopping cancer. God gave the body the ability to heal itself and that it can provided its fed properly. Unfortunately today most people have no idea of what they are consuming and this will keep the cancer rates going up. Overall the cancer death rates remain unchanged in the last 80 years. Western medicine does not treat the cancer but rather the symptoms. The patient is nothing more than a revenue stream. The idea ,keep them alive as long as possible. The medical industry uses terms like remission. That does not mean cured but most make the inference to the patient that they are. Remission means we cant see any cancer. Most doctors do not go after the CTC;s (circulating tumor cells) they should. If not the chances are very good at some point in time the cancer will return with a vengeance.

    Rational Therapeutics chemo sensitivity test makes good sense and yet its never mentioned by doctors to there patients. Is there an insurance coverage problem?

    I would be very interested in any studies conducted on cancer survivors of 20 plus years. To my knowledge none have been done. Gee I wonder why?

    • Iwona Grad says:

      Though I am a big fan of nutrition etc, I think your views are a bit extreme. Doctors first of all want to help patients. They try their best. They have the tool that they have, so they use them. But a lot of progress is being made. The blog entry describes exactly that. Before there were just chemotherapeutics directed at killing dividing cells, the rationale being cancer cells divide fast while majority of normal cells do not (with the above-mentioned exceptions responsible for the drug’s side effects). Now we know more about cancer biology, so targeted therapies are being developed. And so Gleevec was born. 98% cure rate without side effects (or minor ones). So You cannot say that for CML patients the death rates have not changed.

      • There are indeed success stories. Gleevec (Imatinib) is one of the most compelling examples of smart therapy. This is a drug designed to target a specific mutation found on the vast majority of the cells in the CML leukemia populations. As good a story as Gleevec is, it is not one that we have been able to readily reproduce. The next generation of solid tumor “Gleevecs” (as it were) like Gefitinib, Erlotinib, Vemurafinib, Sunitinib, etc. have provided smaller percentages of responders and almost all of them are brief, generally measured in months. More to the point, these drugs are not “growth inhibitors” but instead “survival signal” in inhibitors. Thus, the very example of Gleevec is one that comes from the realm of cell death and not cell growth based therapies.

      • Jim says:

        Drugs will never be the answer in curing cancer. There are many cancer cures available that have been shoved under the rug. If you cannot patented it their is no interest, This has been going on for decades and many of these solutions have been used for various diseases including cancer very successfully for many years. Criminal organization such as the FDA and Big Parma should be eliminated and only then will the open genocide cease. .

    • I presume your final question is rhetorical. Then the answer is, as you suggest simply that there are but a small number of “survivors” to have reached the lofty goal of 20 years. I must tell you that I am a current patient being helped by ‘Rational Therapeutics’, diagnosed 3/05. Durring the first five years we engaged in an all out battle using every tool, most notably surgery and assay directed chemo. It took several cycles to get the cancer into a quiet box. I’m NSCLC so the stats concerning survival for people like me are terrifying yet progress is being made. obviously I am thoroughly biased toward RT and Dr. Nagourney because I know without a doubt, that I would be long dead had I not been fortunate enough to be referred by the friend of an RT patient to them. I have directly experienced the frustration of other of my care providers (doctors) being unwilling to work with RT as part of the team. Why you have asked, simple in my estimation. Ego, ego and then a bit more ego prevents many doctors from admitting they they do not have all of the answers and need additional help. That’s it in a nut shell.
      PS: I really am trying to improve my diet as well: no sugar, no sodas, lots of veggies, so there is hope!

      • Thanks for your post. Long term survivorship is the goal and every story like yours is very rewarding. Physician are increasingly limited in their capacity to think outside the box. They are not rewarded for their successes but are punished for their failures. They find themselves applying the established guidelines (NCCN, etc.) and given stern warnings when they do not. Personalized cancer (laboratory selected) care and standardized (guideline driven) cancer care are on a collision course and the it is the patients who stand to suffer the consequences.

  2. JIM says:

    You will notice I said overall the death rates have not changed. Doctors are allowed to practice within the bounds set by the FDA, NCI W.H.O and many others. Step outside and suffer the consequences. GLEEVEC
    has both serious and mild side effects. 98% cure rate? says who?

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