Why Some Patients Refuse Chemotherapy – And Why Some of Them Shouldn’t

In the June 13, 2011, issue of Time magazine, Ruth Davis Konigsberg described cancer patients who refuse to take potentially lifesaving therapy. Her article, titled “The Refuseniks – why some cancer patients reject their doctor’s advice,” examined the rationale applied by patients who decline chemotherapy. Many of these patients are rational, articulate, intelligent and capable individuals. While there are those who by virtue of religious belief, underlying depression, or loss of loved ones, decline interventions, many of these patients make compelling arguments in favor of their decisions.

When we examine the basis of these patients’ therapeutic nihilism, much of it reflects the uncertainty of benefit combined with the certainty of toxicity. What these patients articulate is the fundamental dilemma confronted by cancer patients, what we might describe as their logical assessment of “return on investment.”

Everything in life is based on probabilities. Will your husband or wife be true? Will you have a boy or a girl? Will you live to see retirement? Will your nest egg be adequate? Cancer medicine is no different.

Will the treatment I’m being offered extend my life long enough to be worth the short- and medium-term toxicities that I will certainly suffer?

While I cannot address this question with regard to surgery or radiation, I feel uniquely qualified to do so in the context of chemotherapy. What, after all, is a chemosensitivity assay? When correctly performed, it is a laboratory test that dichotomizes groups of patients with average likelihoods of response (e.g. 20%, 30%, 40%, etc.) into those who are more or less likely to respond based on the results. On average, a patient found sensitive in vitro has a twofold improvement in response, while those found resistant have a demonstrably lower likelihood of benefit. We have now shown this to be true in breast, ovarian, and non-small cell lung cancers, as well as melanoma, childhood and adult leukemias, and other diseases.

To address the misgivings of the Refuseniks, we might ask the following question: Would you take a treatment that provided a 30 percent likelihood of benefit? How about a 40 percent? 50 percent? 60 percent? 70 percent? Or 80 percent? While many might decline the pleasure of chemotherapy at a 20-30 percent response rate, a much larger number would look favorably upon a 70 percent response rate. On the flipside, a patient offered a treatment with a 50 percent likelihood of benefit (on average), who by virtue of a lab study realizes that their true response rate is closer to 19 percent (based on resistance in vitro), might very logically (and defensibly) decline treatment. These real life examples reflect the established performance characteristics of our laboratory tests (Nagourney, RA. Ex vivo programmed cell death and the prediction of response to chemotherapy. Current Treatment Options in Oncology 2006, 7:103-110.).

Rather than bemoan the uncertainties of treatment outcome, shouldn’t we, as clinical oncologists, be addressing these patients’ very real misgivings with data and objective information? I, for one, believe so.

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.

24 Responses to Why Some Patients Refuse Chemotherapy – And Why Some of Them Shouldn’t

  1. Nydia I. Martinez says:

    I should have been a Refusenick! and I should have known about chemosensitivity tests when presented with the chemotherapy option. Instead, I was prescribed 6 sessions for breast cancer. After the third session, I developed severe neuropathy – to the point of barely being able to walk – Needless to say the rest of the treatment was cancelled. But, a chemosensitivity test may have prevented all of that.

  2. Elaine L. says:

    This isn’t exactly the same issue, but we on the Ovarian Cancer National Alliance, have repeatedly debated when to begin chemo for a recurrence. We’ve read the study indicating that beginning chemo for symptomless disease doesn’t increase overall survival. However, most of us didn’t have any symptoms when we were diagnosed with stage III or IV disease and don’t trust waiting for symptoms to emerge. Some of us want to begin chemo when our CA 125 begins to show a trend (i.e. doubling), while others wait until a CT or PET scan shows measurable disease. Dr. Nagourney, how do you determine when a patient should begin chemo for a recurrence.

  3. Natasha says:

    I’m planning to refuse treatment, because my doctor says this kind of test is unavailable at my HMO. Why risk toxicity when none of the available treatments is a cure? I need my immune system running as long as possible.

  4. Although the EVA-PCD functional profile may not be a covered service by your HMO, you can arrange to obtain a tumor sample (if easily available), analyze your tumor outside of your body and determine whether there are effective, easily tolerated therapies that may provide you benefit. The fact that your insurance does not pay for a particular item or service does not mean that you should not receive it. We would be happy to walk you through the steps to determine whether the EVA-PCD functional profile could be a valid option for you.

  5. elin says:

    i am a breast cancer patient stage II and i had done my mastectomy(total breast removal) this year (2011) and i am just 25 years old.my doctor had suggest me to take chemotherapy and radiotherapy as for further treatment but after my doctor explain to me the side effect of the chemotherapy how ever i refuse to take the chemotherapy. i was thinking that now i’m feeling great and can do my activity life like normal after 1 month from the srugery but i’m not i’ll be able to do so after the chemotherapy.my doctor strongly advise me to continue doing the chemo cos she believe it will expand my life and preventing from the cancer to spread.but my doctor didn’t give her words she just say maybe it would.so now,im taking my own chance of life to continue my life without chemotherapy.

  6. vee greenburg says:

    of all the cancers i see listed, i don’t find any brain tumors, which run on my husband’s side of the family. is this an area you deal with or not?

    • Brain tumors, the most virulent form of which are known as glioblastomas, can be evaluated in the EVA/PCD platform, and we have conducted many studies upon them. Obviously, patients must be candidates for surgery before we can participate in the care, but newly diagnosed and/or recurrent tumors that can benefit from surgical cytoreduction can submit a portion of tumor for study. Among the agents of interest are drugs like BCNU, Temozolomide and Irinotecan. Antivascular agents as well as EGFr and mTOR inhibitors may also be of interest.

  7. Bob Kaiser says:

    I have Merkel Cell cancer. Originating in the Perotid gland. Surgery and Radiation were performed.
    It has now shown up in my abdomen. Everything I have read about this rare cancer suggests that
    chemo is not effective in any of the cases similar to mine. Do you know anything about this type of
    cancer?

  8. kari says:

    I just had a mole biopsy haven’t got results yet hoping they will be good because if I had melanoma I would refuse chemo and radiation I don’t want to be used for testing they don’t Care about u if you die or not I’d rather keep my immune system and live as long as possible and put it in gods hands I’d rather die happy then suffering and in pain and uncomfortable with myself or possibly getting other cancers in the future from taking chemo and radiation btw I am 21 female and I recommend you doing research before making an awful decision of chemo. Goodluck everyone hope I helped a little just putting my opinion out there.

  9. Barbara Thompson says:

    I opted out of chemotherapy for Stage IV colon cancer. I did have surgery and removed half my colon and did very well with that. i then took 8 months of chemotherapy and it was very difficult for me to survive the side effects. In fact, I am left with neuropathy and some stomach problems. Then after completion of the course of chemo, they did a laparoscopy and found that I had tumors in the adnexal region, removed four of the tumors, and left seedlings that they were unable to remove surgically. So the oncologist recommended that I try another chemo treatment since the tumors were resistant to the chemo that I had previously and in fact, grew while on chemotherapy. I took one treatment with Avastin, was deathly ill for 2 1/2 weeks, uncontrollable diarrhea, and had complete hair loss among other very stressful side effects. That is when I decided. NO MORE CHEMO for me. I am now seeing a nutritionist/oncologist who put me on a cancer fighting diet, and exercise program, and supplements, and I feel good and have been doing good for the past six months. I don’t know how long I will go like this, but I feel that the past six months have been just as successful as another chemo treatment would be. I am 70 years old.

    • Dawn Wilson says:

      Hi Barbara, I have had a recurrence of cervical cancer IVB and thinking about refusing the chemo and trying the natural way – would you mind passing on the detail of the nutritionist/oncologist who could advice in terms of a diet and so on ? Thanks, Dawn

  10. TD says:

    My mother has recurrent metastatic endometrial cancer. She had a radical hysterectomy 2 1/2 years ago. The cancer is systemic. She has cancer in her lymph nodes, lungs and breasts. A PET scan indicated that she probably has cancer in other parts of her body. She has severe vaginal pain. Her cancer is inoperable. She is receiving radiation; which, we feel, has been an effective tool as part of her pain management. With oxycodene, oxycontin and radiation her pain has become more manageable. Doctors have been reluctant and/or avoided a prognosis. Multiple doctors have said that her cancers will not be cured, she is in stage 4, and that the cancer was not “caught” early. Doctors have a tendency to use the diagnosis “recurrent metastatic endometrial cancer,” as if that tells us everything we need to know, or that this is somehow synonymous with a prognosis. Looking up the diagnosis online, no need for arguments for/against getting information this way, it seems unanimous that my mother has between 9 and 14 months in all “likelihood.” Perhaps there is comfort in statistics and percentages for some, not for me… I’d like someone to use words that mean something. Only one doctor has used the term “prolong life.” But, it seems we are still talking a about a year at best. We are now at the stage of adding chemo. Chemo seems like it will add as much or more pain and/or discomfort. I’m concerned that she will prolong her misery more than prolong “life.” She is looking to me to make decisions and/or tell her what to do. What to do?

    • Sorry for the delayed response.

      Every cancer patient is an experiment in real time. In the current milieu there are no “likelihood’s of response or survival” just average expectations. At the beginning of every race, each participant has a chance of winning but only one will actually cross the finish line first. Every patient manifests a unique profile that propels them to the finish line. Winner or loser, we cannot, with certainty, say until the race is run. However, our laboratory tries to give every patient some idea as to how they are likely to fare in the long run. Is chemotherapy effective? Is one combination better than another? Is it worth taking therapy or better to avoid the toxicity and time spent? No test is perfect but on each of these accounts we can approximately double the accuracy of the determination.

      Endometrial cancers are not dissimilar to ovarian cancers in their response to therapy. If we can apply our experience in this closely related disease to assist your mother, we may indeed be able to help. We would be very happy to try.

  11. David says:

    I am a 63 yr old male with Stage IV metastatic melanoma with no primary source. After lung lobectomy, and lobe resection, along with 27 ‘abnormal’ lymph nodes removed, chemo was called for. I also have rheumatoid arth. I have refused the chemo. The oncologist argues a prolonging of life; but, until he can give me date certain of his death, how can it be said that he can prolong mine. After all, when we were popped on the behind at birth, we started dying. Thank you.

  12. Ablahanan says:

    Dr. Nagourney, I am not appreciative of your term “refuseniks”. It is patronising and condescending when used in reference to individuals being dealt the rather poor choice “poison or death?” don’t you think? The reasons you give for these mostly “intelligent” human beings declining is the no guarantees of success rate. There are other reasons, many, not the least of which is that chemo is known to diminish the immune system and also that studies show that cancer returns after chemo at a later date in a more aggressive and resistant form. True? What would you do if you were in the hot seat, I wonder. Illness doesn’t always happen to others. I am an amateur, of course, and you are highly educated, well-informed and experienced. To lighten this up, I, personally, would rather be prescribed an overdose of propofol than chemotherapy but I guess that’s not on offer! Keep on saving people’s lives, thanks for those you have.

    • robert nagourney says:

      I used the term “Refusenik” only in the context of the article from Time magazine, in which Ruth Davis Konigsberg described cancer patients who refuse to take potentially lifesaving therapy. Her article, titled “The Refuseniks – why some cancer patients reject their doctor’s advice,” was the basis of my blog topic.

      I did not intend to offend anyone and did not choose the term. It was the subject and title of her article. My point being that in the absence of objective data upon which to make sound judgments, patients my take more treatment than they need or decide against therapies that might be helpful simple because they have so little to go on.

      • Ablahanan says:

        Thank you for clarifying that, Dr. Nagourney, and also for your rapid reply. I hope that patients will take the time to educate themselves. You work in a very difficult field but with God’s will, you will save many lives.

  13. Robert B. says:

    Hello, I was diagnosed with colorectal cancer in march and the tumor was removed august 8th. My oncologist wants me to start 6 cycles of more chemo at a higher rate than I was taking in the radiation/chemo treatments prior to surgery. Since the tumor was removed and no other indications of cancer are present via biopsies from surgery, also, the tumor was a stage 2 contained, why do I require six more cycles of a higher dosed chemo treatment? Seems like an overkill to me. Robert

    • My presumption is that this is rectal cancer. This disease is generally treated with chemotherapy plus radiation. This provides “radio potentiation” but the doses are usually lower than they would be for single modality chemotherapy.

      If at the time of surgery there is evidence of viable tumor (termed ypTNM) for post treatment staging, then we often proceed with additional post op chemotherapy at full dose known as adjuvant therapy. Again, I do not know the particulars of your case but this sounds like the most logical case from what you have described.

      • Robert B. says:

        This is colorectal cancer : the tumor has been removed and there is no cancer indicated in the biopsies as the cancer tumor was contained within the colorectal canal.
        :
        Thank you so very much for your thoughts and comments. I have had both chemo at 2600mg per day and radiation treatments five days per week for seven weeks prior to the operation. There was then six weeks off without treatment prior to pre=opp, thence the operation August 8th. It is now six weeks since the operation and I am slowly healing from the outside inwards. I also have a enlarged prostrate not uncommon for my age of 69 which will also be operated upon pursuant to my tummy operation to re engage the intestines. My question lies with the additional chemo treatment of six cycles which encompases eighteen weeks for what purpose. There are NO indications of cancer from the CT scan, nor the MRI, nor from the biopsy from the operation. This delays my body being returned to a somewhat normal stage by 18 weeks for what purpose….. I truly believe this is an over kill. If for one second there was an indicator of cancer anywhere, I would not question the direction. There is NO such indicator. Please also note that the six cycles of chemo are at a higher rate of 3,00 mgs per day from the previous2600.

        Respectfully, your thoughts.

        Thank you, Robert

  14. Robert B. says:

    Thank you for your response to my question. I have added more information for your review of my initial question/concern. Please advise further your thoughts. Thank you. Robert B.

    • Robert,

      Each patient’s treatment reflects the physician’s consideration of the case, from pathologic findings, to initial stage, grade and other features. While there is good data to support the use of post operative adjuvant chemotherapy for patients with persistent disease after neo adjuvant therapy, the use of chemotherapy post operatively in a patient with a complete remission would be a decision that would be made with your treating physician within the totality of your clinical case.

      • Robert B. says:

        Thank you so very much for your pertinent comments and timely at that. My surgeon has basically agreed with me with regard to the chemo aspect and I am now in the final 3 stages of returning my body to a normal function. Your comments have given me comfort in the determination I have made in NOT having
        the six cycles of chemo. I do not have the medical knowledge but I do have the ability to rationalise what I think is right. While You do not have specific into my case, I do appreciate your medical comments related thereto. I will keep you posted on my progress back to a more normal life style.

        Respectfully,

        Robert B.

  15. Laura says:

    Thank you for the article. I had breast cancer and I also refused the chemo. According to statistics found on the predict and adjuvant websites it “might” only add 8 to 12 percent increase in survival. For me that wasn’t significant enough for the risk chemo involves. However, as your article points out, if it would have added 70 or 60 percent or some number of significant size to my outcome I would have reconsidered.

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