Not many MDs, least of all an oncologist, would dare to break ranks from the rules of the medical establishment and especially from the clutches of Big Pharma in the present day cancer industry. One exception is Dr Otis Webb Brawley, MD, and oncologist and the Chief Medical and Scientific Officer and Executive Vice President of the American Cancer Society.

As we were reading the 2011 best seller in America “HOW WE DO HARM” by Dr Brawley, we were shocked to read in Chapters 6 and 7 that Erythropoiesis-Stimulating Agents (ESAs) causes tumour promotion i.e. the anemia-building drugs seemed to be encouraging tumors to grow.

 What Are ESAs?

Erythropoiesis-stimulating agents are one of the most common drugs used to treat anemia i.e. these are medication that increase the production of red blood cells. For a brief introduction, go to: http://www.anemia.org/patients/feature-articles/content.php?contentid=000379

The doctor would give you ESA or a blood boosting injection if you do not enough blood after a chemo treatment. They use “the red juice” to fight anemia by stimulating red blood cell production and “the white juice” to fight neutropenia, a deficiency of white blood cells.

If these ESAs or “hemoglobin-building” drugs are supposed to perform a useful function in overall cancer treatment, why then is Dr Brawley so vociferous against these drugs? He even mentioned that “these drugs stimulate cancer growth”

Let us examine some of the reasons:

• The FDA approved the drugs for the treatment of anemia in cancer patients in 1993 based on data pooled from only 6 small studies that altogether enrolled a total of only 131 patients (page 76).
• The 6 minuscule trials… asked only whether Procrit (one of the ESA drugs) had the ability to prevent blood transfusion. Not a shred of data said anything about “fatigue” or its opposite “strength” (page 77).
• There were a lot of unanswered questions such as: was their anemia corrected? Did their underlying cancer recur? Did they die sooner? Did they face a higher risk of blood clots? (page 77).

Soon after hemoglobin-drugs were approved, a German radiation therapist named Michael Henke decided to test one of the fundamental tenets of his subspecialty: that patient with higher hemoglobin levels have better responses to radiation therapy. Henke believed in the connection between hemoglobin and response to radiation. However the study’s results didn’t come out the way Henke expected. The result of Henke’s study, which was initiated in 1997, was published in 2003. The study showed that patients who received the hemoglobin-building drug didn’t live as long as those on placebo. Also, the disease progressed more rapidly in patients receiving the drug. Henke concluded that he had encountered a biological phenomenon: the drug seemed to be encouraging tumors to grow (page 81).

In August 2003, researchers had to stop another study, the Breast Cancer Erythropoietin Survival Trial (BEST), when more women died on Procrit than on the control arm. In both the Henke trial and BEST trial, the survival curve showed an increased risk of death from cancer, which suggested something you don’t want to see in patients you are treating for cancer –  tumour growth (page 82).

In other words, pharmaceutical companies were promoting an untested therapy that was supposed to make patients feel better and stronger when, in fact, it caused stroke and heart attacks and in some cases made tumors grow (page 73).

According to Dr Brawley, FDA approved these drugs to reduce the risk of blood transfusion in patients with solid tumours treated with chemotherapy. That’s it. Not a word was said about “tiredness”, not a word about “cancer fatigue”

In Chapter 6, Red Juice and Chapter 7, Tumour Progression, Dr Brawley described how cancer patients are routinely “offered” hemoglobin-building drugs to even borderline anemia, a common side effect of cancer drugs. The drug companies manufactured a medical condition called “cancer fatigue” and nurses were trained to “suggest” “erythropoiesis-stimulating agents (ESA)” to all patients undergoing chemotherapy – “the red juice” to fight anemia by stimulating red blood cell production and “the white juice” to fight neutropenia, a deficiency of white blood cells.

• With powerful incentives set in motion, many hospitals and oncology practices in the US instructed nurses to ask leading questions about “fatigue” with the intent of expanding sales to a growing number of patients and upping the dosage to each patient. This is referred to as “an ESA treatment opportunity”
• These drugs are still being prescribed routinely. According to Dr Brawley,” these ESA drugs were not used to cure disease or make patients feel better. They are used to make money for doctors and pharmaceutical companies at the expense of patients, insurance companies and taxpayers “(page 97)
• Also the disease progressed more rapidly in patients receiving the drug (page 81) i.e. the drug seemed to be encouraging tumors to grow…this compound is a stimulant, a “tumor fertilizer”. A patient with active disease is more likely to suffer tumour progression: the more tumor you have, the more tumor there is to stimulate!! (page 97). 

• Commenting further on ESA drugs, some doctors didn’t bother to check what the patient’s hemoglobin was and erred on the side of giving the ESA every time they give chemotherapy. Doctors routinely prescribed the drugs for uses in which it had not been studied-such as anemia caused by cancer itself, as opposed to anemia caused by chemotherapy (page 78).

Besides Dr Brawley’s comments in the book, we searched further for sound scientific validation of ESAs causing tumor promotion. These are extracted from prominent sources like the FDA, Journal of Clinical Cancer Research, Annals of Oncology, British Journal of Cancer, PubMed Medline, Journal of Oncology Practice, etc. There are lots more. The following are some of the links you may be interested to read:

1)      THE FOOD AND DRUG ADMINISTRATION (FDA) of the US issued a Drug Safety Communication dated 26/2/2010 under the following title: “Erythropoiesis-Stimulating Agents (ESAs): Procrit, Epogen and Aranesp.”

In the article, the FDA warned that cancer patients using ESAs should understand the risks associated with the use of ESAs. These risks include:

• ESAs may cause tumors to grow faster.
• ESAs may cause some patients to die sooner.
• ESAs may cause some patients to develop blood clots, and serious heart problems such as a heart attack, heart failure or stroke.

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm

2)      In July 2011, THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, in its journal, Clinical Cancer Research published an article entitled: “The Role of Erythropoietin and Erythropoiesis-Stimulating Agents in Tumor Progression” It reported that:

• Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia [chemotherapy-induced anemia (CIA)].
• Recent clinical trials have reported increased adverse events and/or reduced survival in ESA-treated cancer patients receiving chemotherapy, potentially related to EPO-induced cancer progression.

 http://clincancerres.aacrjournals.org/content/17/20/6373.abstract

3)      THE EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY in its journal, Annals of Oncology (2010) published the following guidelines: “Erythropoiesis-stimulating agents in the treatment of anemia in cancer patients: ESMO Clinical Practice Guidelines for use.” The lead author, Professor Schrijvers, although on the Advisory Board of Johnson and Johnson admitted the following:

• The influence of ESAs on tumour response and overall survival in anemic cancer patients remains unclear. Several randomized trials have demonstrated decreased survival times and poorer loco-regional control or progression-free survival 
• Other recent meta-analyses showed that ESAs increase and worsened overall survival when given to cancer patients. 

 http://annonc.oxfordjournals.org/content/21/suppl_5/v244.full

4)      In September 2007, THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY published the following article in its Journal of Oncology Practice: “Erythropoiesis-Stimulating Agents: Continued Challenges” in which:

·         The FDA revised both the epoetin alfa and darbepoetin alfa product labels, with new “black box” warnings and expanded information on safety, tumor progression, and survival.

·         Additionally, the new warning states that ESAs are not indicated for patients with active malignant disease receiving neither chemotherapy nor radiotherapy.

 http://jop.ascopubs.org/content/3/5/248.full

5)      In March 2012, THE BRITISH JOURNAL OF CANCER (of the CANCER RESEARCH of UK) published several research studies done on the usage of ESAs and concluded that….”several trials have reported an association between ESA use and increased disease progression and/or mortality” The article is entitled: “Effects of erythropoietin receptors and erythropoiesis-stimulating agents on disease progression in cancer”

 http://www.nature.com/bjc/journal/v106/n7/full/bjc201242a.html

In another book, A WORLD WITHOUT CANCER, Dr Margaret Cuomo, a radiologist also stated that… “even drugs used to treat the side effects of chemotherapy have been linked to secondary cancers”. For example, patients who need medication to raise their white blood cell counts may be injected with granulocyte colony stimulating factor (G-CSF), a substance normally found in the blood. Researchers observed that this doubled the risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML)… (page 69)

READ THE FOLLOWING LINKS FOR MORE INFORMATION ON MDS/AML: 

1)   THE STORY OF ROBIN ROBERTS:

http://abcnews.go.com/Health/robin-roberts-myelodysplastic-syndrome-diagnosis-beat/story?id=16540293#.UZnTWaKLC-U

2)   In 2007, THE NATIONAL CANCER INSTITUTE (US) published the following article in its Journal (JNCI J Natl Cancer Inst Volume 99, Issue 3 pp. 196-205).…. “Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors during Breast Cancer Adjuvant Chemotherapy” The article concluded that….”the use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied”……

http://jnci.oxfordjournals.org/content/99/3/196.short

FOOTNOTE: In Malaysia, these ESAs (and G-CSF) are commonly referred to as “booster” or “booster jabs” and are generally given after the 3^rd or 4^th cycle of chemotherapy when the patient’s RBC, WBC, Platelets, Hemoglobin, etc are low. These booster jabs are costly…..and that is why patients are warned not to use cheaper and (safer) methods (because it will clash with the chemo drugs!!)

A POINT TO PONDER UPON:

When a patient decides on chemotherapy treatment, he or she expects to be healed and not to have the cancer spread or suffer second malignancies shortly after completion of the scientifically tested and proven treatments. And to be given ESAs or G-CSFs which later promotes tumour growth isn’t it too much for the patients to bear? Is this a double bonus or a double whammy for the patients? (Please note we have not factored in the damaging side effects of radiotherapy into the above scenario).

We welcome your views.