Abstract: After surgery, microscopic cancer cells are still left behind in the body. As an insurance policy (“just in case”), cancer patients are usually advised to undergo chemotherapy or radiotherapy. The idea is to kill whatever cancer cells are left behind. How valid is this assumption that chemotherapy can just do that? Cancer patients are often very baffled that, after spending a vast amount of money on such “evidence-based” conventional treatments, they either experience a recurrence within a short period or there is metastasis to other parts of the body like the lungs, bone, liver etc. Why does this happen if the chemotherapy drugs that have been given are claimed to be scientifically tested/proven, FDA-approved, latest state-of-the-art type?
Yeong Sek Yee & Khadijah Shaari
10, Jalan SS 19/1K, 47500 Subang Jaya, Selangor.
Tel: 03-56342775 / 019-3278092
After surgery, microscopic cancer cells are still left behind in the body. As an insurance policy (“just in case”), cancer patients are usually advised to undergo chemotherapy or radiotherapy. The idea is to kill whatever cancer cells are left behind. How valid is this assumption that chemotherapy can just do that? Cancer patients are often very baffled that, after spending a vast amount of money on such “evidence-based” conventional treatments, they either experience a recurrence within a short period or there is metastasis to other parts of the body like the lungs, bone, liver etc. Why does this happen if the chemotherapy drugs that have been given are claimed to be scientifically tested/proven, FDA-approved, latest state-of-the-art type? To understand this phenomena better, we search various books, literature on cancer and cancer treatment written by medical doctors, oncologists, cancer researchers, scientists, professors of medicine, etc to try to understand the reasons why cancer patients may not respond to chemotherapy.
This is summarised in the ensuing pages … please read on and find out more why chemotherapy drugs may not work for you, what is chemo drug resistance, why chemo resistance develops, what is half-life of a drug, why a person made toxic by chemo drugs is more likely to suffer recurrence of the cancer later on, why chemotherapy combinations causes cancers to grow and spread much faster than would ordinarily occur, etc.
There may be a lot of information that your doctor/oncologist may not have explained to you (other than …”this is the latest drug, scientifically tested, evidence-based, targeted therapy, etc, etc). Find out more and evaluate your options.
1)FIGHTING CANCER WITH KNOWLEDGE & HOPE by Dr. Richard C. Frank, MD, an oncologist who is the Director of Cancer Research, Whittingham Cancer Center, Norwalk Hospital, Norwalk, CT, and Medical Director, Mid-Fairfield Hospice, Wilton, CT.USA. THIS BOOK WAS PUBLISHED IN APRIL 2009.
As expected, the whole book is devoted mainly to describing the virtues of conventional treatment of the various types of cancers via surgery, radiation, chemotherapy, targeted therapies and hormone therapies. However in the chapter on “How Cancer Grows and Cancer Treatments at Work”, Dr. Frank gives an explanation as to why chemotherapy may not work for you. We summarize the main points below:-
CANCER CAN GROW UNPREDICTABLY (pages 124-126)
a) Although cancer appears to develop in an organized fashion when viewed from the outside, if we were to go inside a tumour with a little magnifying glass and monitor the movement of cells and the integrity of DNA; we would see a much more chaotic situation.
b) As a cancer develops and grows, the DNA that guides it along is prone to change…. as a cancer grows, its genetic makeup becomes diversified, which leads to a diversity of cell types within it…. cancer is not a collection of identical cells.
c) The tendency of a cancer to generate cells with different capabilities explains many of the dreadful aspects of cancer that patients find so hard to grapple with:
• Why it can spread from one location to another,
• Why it stops responding to a treatment that was working,
• Why it can return when it was in remission
The reason is that every cancer, whether it arises in the lung, breast, prostate, bone marrow, or elsewhere, contains different populations of cells that have distinct properties.
d) A cancerous tumour does not contain billions of identical clones. Cancer could never develop in this way because it must avoid the immune system’s attack on it, live in areas of low oxygen tension, and compete with the rest of the body for vital nutrients.
e) Inside any tumour are cells that are living and cells that have died. There are cancer cells capable of reproducing many others, called cancer stem cells, and cells completely devoid of this capacity. Cancer’s diversity is generated early. By the time it is diagnosed, some cells may already be capable of metastasizing and others may be able to withstand a particular cancer treatment. This is the basis of cancer’s resistance to treatment i.e. chemotherapy (see section “Why Do Cancer Treatments Sometimes Fail?”).
f) When new cancer cells are generated inside a tumour, some will be hearty enough to survive and others will not be. If some cells survive the treatment, then it is mainly because their DNA contains the necessary alterations that help them resist the chemotherapy drug; this population of cells will then expand, and the compositions of the cancer will again change. (page 126)
g) …. when a cancer returns after being declared in complete remission, it is because a few cells were different enough to stay alive after a treatment killed nearly all the other cells; this difference could have been present from the start of treatment or it could have developed as a response to it. Whichever occurred, it is cancer’s ability to diversify and adapt its DNA that enables it to survive. (page 126)
WHY DO CANCER TREATMENTS SOMETIMES FAIL?
(a) Drug resistance or the growth of cancer in the face of ongoing or recently completed treatments represents the main barrier to cure for many cancers…. (page 188). In many instances, oncologists cannot specify why a person’s cancer develops treatment resistance…. treatment resistance is probably the most complicated area of oncology. (page 189).
(b) The root cause of a cancer relapse lies in the fact that cancer is not an accumulation of exactly the same cells but rather a mixture of cells with differing properties. Some may have sensitivity to certain drugs and be killed by them, whereas others are resistant to those drugs. The resistant population will survive treatment and in time be detected as a cancer relapse. (page 189)
(c) Drug resistance may be present in an untreated cancer or emerge in response to therapy…. the innate adaptability of cancer cells and how they can sometimes outwit an effective therapy by altering their DNA or other molecules. This property explains the acquisition of resistance during a cancer’s growth. (pages 189-190)
(d) Chemotherapy may lose its effectiveness when cancer cells activate a protein that pumps the drugs out as soon as they enter the cells; targeted therapies may lose their ability to control their targets when those receptors and signalling proteins mutate and morph into different shapes; hormone therapies may stop controlling cancer growth when estrogen or androgen receptors undergo a shape change or get massively overproduced, overwhelming the drugs meant to neutralize them. (page 190)
(e) Several types of cancer have been found to contain a very small population of cancer stem cells, which are believed to be responsible for continually replenishing the pool of cells in a tumour. It turns out that an additional property of these cancer stem cells is their natural resistance to chemotherapy and other cancer treatment.
(f) Some chemotherapy drugs (as well as radiation therapy) may contribute to (or directly cause) the development of new cancers many years after treatment (page 174). And it has been known for decades that chemotherapy alone cannot eradicate the advanced stages of the most common cancers (page 175).
TARGETED THERAPIES: The current hot trend is to offer targeted drugs like Erbitux ( for colorectal, head and neck cancers), Rituxan (for lymphoma), Herceptin (for breast cancer), Tarceva (for lung cancer), Sutent (for kidney cancer) and etc. Once in the bloodstream, they act like heat-seeking missiles, locating cancer cells wherever they lurk and gripping onto them via one specific receptor target (among thousands of receptors) that projects from the outer surface of the cells. The result is that the receptors stop transmitting growth signals inside the cells (page 177).
(a ) Are targeted therapies “magic bullets”?
According to Dr Frank …..” although targeted therapies were developed with the hope that they would be magic bullets that would neatly eradicate cancer through selective targeting of one critical molecule, in general they have fallen short of this lofty goal. No cancer is considered curable by treatment through a targeted therapy alone… (page 180) The reason for the muted success of targeted therapies is that most cancers are caused not by one genetic derangement but by several; no one target functions as an Achilles heel. “(page 180)
(b) Do targeted therapies cause side effects?
“Like any other drug taken for any purpose, unintended effects may occur with these medications. Generally speaking, targeted therapies are easier to tolerate – less hair-loss, smaller declines in blood counts, less nausea… still, substantial side effects may occur with some targeted therapies, and they tend to increase the toxicities of chemotherapy when used in combination.” (page 182)
Finally, angiogenesis inhibitors (like Avastin, Sutent, Nexavar, Thalomid) constrict blood vessels not only inside tumours but also in other parts of the body. As a result, they often cause some degree of high blood pressure and are associated with an increased risk for kidney damage, bleeding, stroke and coronary artery blockage. (page 183)
In conclusion, we quote two very relevant statements by Dr. Frank:-
i. Efforts to blast away metastatic cancers with mega doses of chemotherapy have fallen short because they do not root it out but rather cause more harm than good: the cancer is still present and the patient is sicker than ever. (page 143)
ii. Even though billions of dollars are invested in cancer research every year, most new drugs in the research pipeline will extend life rather than the silver bullets that pierce the heart of cancer. (page 145)
2) SURVIVING THE CANCER SYSTEM by Dr Mark R. Fesen, MD, FACP, an oncologist and internist with 15 years of clinical practice and was trained at the National Cancer Institute, US and is currently a Clinical Assistant Professor at the University of Kansas. THIS BOOK WAS PUBLISHED IN APRIL 2009.
As expected, Dr Fesen, with such credentials, did glorify the cancer system (or the cancer industry) in the whole book. However, he did admit (perhaps he can’t run away from the inevitable) that chemotherapy has its limitations (as also admitted by Dr Richard Frank, MD in FIGHTING CANCER WITH KNOWLEDGE & HOPE–as reviewed above).
What are these admissions by Dr Fesen? The main points are:-
a) Rarely do oncologists provide patients with in-depth information about how chemotherapy works. (p97)
b) Adjuvant chemotherapy is similar to an insurance policy. This means that doctors expect to improve the chances that the surgery may have already cured you. (p100)
c) … only a rare handful of cancers are currently curable with only one chemotherapy drug. One rarely, if ever, kills 100% of rapidly dividing cancer cells. For this reason, combinations of chemotherapy drugs are the cornerstone of treatment (p98)
d) Testicular cancer and lymphoma are examples of types of cancer that are especially sensitive to chemotherapy. Unfortunately, for most other cancers, chemotherapy can, at best, only kill a much smaller number of cancer cells inside you. (p101)
e) But remember, even as you are being treated with chemotherapy, the cancer will try to grow. Many chemotherapy drugs are most effective and at their highest concentration for several days after treatment is received-only*The drug may be out of the system and can’t be detected in the bloodstream, but its effects on the body and system remain.* Because many chemotherapy drugs affect your blood counts, they also can’t be given too often. At this time, the cancer may resume growing as you and your body and blood counts recover. (p102)
NB:* Read about Half-Life of Drugs (read NATURAL STRATEGIES FOR CANCER PATIENTS by Dr Russell Blaylock)
f) Thus, each cycle of treatment may result in only a small decrease in the total number of cancer cells inside you. Or your condition may become a stalemate with the rate of cancer cells dying being equal to the growth rate of the cancer. This explains why it may take many cycles of treatment to gain control of your cancer. (p102)
g) Re-treating cancer is not nearly as easy as treating it the first time. Treating someone who has previously received chemotherapy is far more challenging. This is because your cancer develops drug resistance. The initial cancer that is presented is usually populated with relatively sensitive cells. The cancer that recurs after your treatment has been stopped for a while is usually heavily populated with resistant cancer cells (p102)
In conclusion, let us quote another paragraph on chemotherapy by Dr Fesen (see page 97)
“For many, chemotherapy ranks only slightly behind cancer itself as something to dread. Many simply refuse treatment and would rather choose death. Patients truly believe that their quality of life will be better by suffering the effects of advancing cancer instead of receiving chemotherapy. It has been widely known that most common cancers, such as lung cancer, pancreatic cancer, and throat cancer, have been very difficult to treat. For this reason, oncologists have pushed the doses of chemotherapy ever and ever higher to the very limits of human tolerability. Unfortunately, oncologists have not always made the tolerability of chemotherapy treatment a high priority. Often patients suffered severe side effects, including heart damage, lung damage, near fatal infections, kidney failure, extreme nausea, and vomiting”.
3) LIFE OVER CANCER by Dr Keith Block, MD, Director of Integrative Medical Education at the University of Illinois College of Medicine and Medical Director of the Block Center for Integrative Cancer Treatment in Evanston, Illinois. A conventionally trained Hematologist and Oncologist who also studied acupuncture, herbal medicine, nutrition and homeopathy. THIS BOOK WAS PUBLISHED IN APRIL 2009.
In the chapter on Oxidation (chapter 14) Dr Block explained “why chemotherapy and radiation are not more effective against cancer” and we quote below his full explanation.
“Radiation and many chemotherapy drugs kill malignant cells by generating lethal oxidative stress. That is, they generate such an avalanche of free radicals that the cells are destroyed. The problem is that there are always some survivors. Cancer cells that are exposed long-term to free radical levels that are high, but not enough to kill them, adapt. In a perverse case of Darwinian “survival of the fittest” some cancer cells may mutate in a way that makes them more and more resistant to treatment. It is very much like mosquitoes developing resistance to DDT: survivors of the initial spraying become invulnerable to the poison, and their offspring inherit the same resistance until the entire population shrugs off DDT. So it is with cancer cells. If even a few develop resistance to treatment, all of their descendants have it, too. ( page 304)
Failure to target the biochemical terrain….. is one reason we have been losing the “war on cancer”…. Although the drugs shrink or even (apparently) eliminate the tumor, they often do not improve patients’ survival. How can this be? Surely if your tumour is gone, or a lot smaller, you have a better chance of survival. Unfortunately, it turns out that as long as the original cancer-coddling biochemical environment remains unchanged, cancer can-and often does-come back in full force. Not only can tiny numbers of residual cancer cells grow back into a tumor, but both chemotherapy & radiation produce enormous numbers of inflammatory molecules and free radicals that promote the growth of malignant cells and blunt the effectiveness of these same conventional treatments. Since cancer uses the body’s own resources to grow and multiply, we must use every aspect of your internal biochemistry to rein it in. Only by transforming the conditions that allow cancer cells to thrive can we hope to overcome the disease, especially over the long term…(page 285-286)”
This is why it is so important to alter your oxidative environment otherwise the terrain is right for the cancer to come roaring back after treatment, even to evolve into a more aggressive form. Indeed, cancer’s ability to continually adapt is one reason why chemotherapy and radiation are not more effective against cancer: the treatments also produce free radicals that support the disease process, allowing any cells that survive the barrage of radiation or chemo to thrive (page 304)
NB: A body with high levels of free radicals is said to be under oxidative stress, one of the key aspects of a terrain that nourishes cancer. Briefly the main oxidative offenders are tobacco & alcohol consumption, sedentary lifestyle and excessive body fat, psychological stress, ionizing and non-ionizing radiation, high storage levels of iron as ferritin, usually due to chronic inflammation or overconsumption of dietary iron (page307)
Dr Block also explained another interesting point why chemotherapy causes more problems than being an effective therapy….”Chemotherapy produces its own set of inflammatory side effects, such as lethargy, sleepiness, loss of appetite, and increased risk of deep vein thrombosis, hemorrhaging, clotting, and hand-foot syndrome. The last is a painful inflammatory disorder that causes swelling and peeling of the skin on the extremities. These side effects are caused by several different mechanisms that increased production of inflammatory molecules called cytokines produced when chemotherapy switches on certain inflammation-producing genes. A 2008 study showed that chemotherapy resulted in high levels of inflammatory molecules such as VEGF or interleukin-6 in some patients (page 328/329)”
4) CANCER AND ITS MANAGEMENT by Dr Robert Souhami and Dr Jeffrey Tobias. Professor Souhami is Dean of the Faculty of Clinical Science and Professor of Oncology at University College London Medical School and Professor Jeffrey Tobias is Professor of Cancer Medicine at University College London and Consultant in Oncology at the Meyerstien Institute of Oncology Middlesex Hospital, London.
The subject of resistance to cancer chemotherapy can be read from pages 70 to 76. Briefly, the main points are:-
a) One of the unexplained phenomena of cancer chemotherapy is that some tumors are generally sensitive to drugs while others are resistant. This inherent sensitivity or resistance extends to drugs of many different classes and mechanisms of action (page 73).
b) The degree of response in an individual to a drug depends on constitutional factors that control drug absorption, distribution and metabolism of the drug before it reaches the tumor. The efficiency of these processes is affected by genetic differences in individuals, which lead to changes in the structure of proteins that are responsible for these functions. (page 72)
c) The cells in a solid tumor are not uniformly sensitive to cytotoxic drugs before treatment starts. Genetic instability develops as cancers grow and somatic mutation causes heterogeneity with respect to resistance to drugs. This provides a partial explanation for greater drug resistance in large tumors where this process has progressed further. As the tumour grows the frequency of development of resistant cells increases so that large tumours have a greater number of intrinsically resistant cells (page 73).
d) Multidrug resistance—this is a membrane of glycoprotein (p-glycoprotein, pgp) which acts as a drug efflux pump reducing the intracellular concentration of some, but not all cytotoxic agents.Its presence confers relative resistance to a series of cytotoxic agents such as vinca alkaloids, anthracyclines… There is clinical evidence that pgp expression in tumors correlates with worse prognosis. (page 73)
e) Attempts have been made to time drug administration in such a way that the cells are synchronized into a phase of the cell cycle which renders them especially sensitive to the cytotoxic agent (page 70). (QUESTION: IS THIS BEING PRACTISED IN MALAYSIA?). However, most drug schedules are not devised on the basis of cell kinetics or synergy but on the basis of toxicity and practicability (page 71).
In conclusion, the authors explained what cancer chemotherapy has achieved. “The majority of curable cancers are uncommon tumors such as childhood cancers, leukemias, lymphomas, and testicular tumors. Other cancers are partially responsive but the impact of chemotherapy on survival is relatively small. The other cancers include cancer of the breast, SCLC, ovarian cancer and cancer of the colon” (page 75).
5) ONCOLOGY by Professor Ann Barrett, MD (Professor of Oncology, University of East Anglia), Professor Chris Twelves, MD (Professor of Clinical Cancer Pharmacology, University of Leeds) and others.
In chapter 6, Systemic Therapy: Chemotherapy and Biological Therapy, the authors touch on CHEMORESISTANCE and their comments as follows:
“Some cancers are resistant to chemotherapy from the outset. For others chemotherapy may induce a partial or even complete response but the tumour re-grows with disease that has become chemo-resistant. Increasingly it is recognized that the ability of cells to either repair or tolerate the damage inflicted by chemotherapy may lead to chemo-resistance” (page 39)
6) COPING WITH CHEMOTHERAPY AND RADIATION by Dr Daniel Cukier, MD , FACR and Dr Frank Gingerelli ( both doctors are radiation oncologists).
Some cancers are very sensitive to one chemotherapy drug, but not sensitive to others. Certain cancers may not be sensitive to a particular drug at a lower dose but may be sensitive to the same drug at higher doses. Sometimes cancers may start out being sensitive to a particular chemotherapy drug, but after several treatments, the cancer cells develop resistance to that drug thereby rendering it ineffective. (page 15).
7) WHAT YOU REALLY NEED TO KNOW ABOUT CANCER by Dr Robert Buckman, MD., a Medical Oncologist, in collaboration with the specialists at MD ANDERSON CANCER CENTER.
a Cancer cells in clumps behave differently from cancer cells growing in a flat layer in a dish…. when there are clumps of cells, they organize themselves and may be capable of resisting or disposing of chemotherapy drugs (page 270).
b) Chemotherapy drugs (or most of them) damage anything in the body that is undergoing active growth and divisions. If the cancer cells are sensitive to the drugs, the effects will be more beneficial. If the cancer cells are resistant to chemotherapy, the effects will be less beneficial or even absent (page 221).
c)….cancer cells are unfortunately very similar to our normal cells, and this makes them very difficult to kill with drugs..(page 221).
8) THE JOURNEY THROUGH CANCER by Dr
Jeremy Geffen, MD, a Board-Certified Medical Oncologist and a fellow of the American College of Physicians.
Chemotherapy has 3 fundamental limitations: side effects, eventual drug resistance by cancer cells, and the inability to reach every cancer cell in the body. (Page 50)
a) Side effects- they’re well known……..
b) Drug resistance- cancer cells can sometimes have very devious and efficient ways of resisting the effects of chemotherapy, known as drug resistance. Over the years, oncologists have employed a number of different strategies to overcome this problem, with only limited success. Another aspect of the problem involved the fact that cancer cells may sometimes become resistant to chemotherapy drugs even if they initially responded to them very well. This is one of the reasons why it can be so hard to actually cure cancer–especially solid tumors–with chemotherapy. If one single cancer cell is not killed by the therapy it can grow back and cause more problem. (Page 56, 57)
c) Chemotherapy’s inability to reach every cancer cell in the body–this occurs in two major ways:
i) First some tumors grow so large that blood vessels no longer carry blood to their deepest innermost regions. Since chemotherapy is carried in the blood, it sometime can’t reach all of the cancer cells that are buried deep inside the tumor. When this happens, those cancer cells survive and can continue to grow, spread to other sites in the body, and develop more resistance to chemotherapy, as described above (page 57).
ii) The second way this problem occurs involves what are called tumor sanctuaries. These are special areas of the body that are naturally protected from the effects of drugs and toxins in order to keep us well. The 2 most important areas that are considered to be tumor sanctuaries are the testes and the brain. When cancer cells are found in these organs it is hard for chemotherapy drugs to reach them, and cancer will re-grow there if not treated with some other means, such as surgery or radiation (page57).