Chemo Con Manipulating Statistical Figures

How Chemotherapy Results Can Be Made to Look Successful

By Cancer Monthly on December 10, 2007 9:48 AM | Permalink | Comments (0) | TrackBacks (0)

Responses and Survival are Not the Same

Response Rates

When discussing the success of chemotherapy in helping cancer patients, oncologists typically discuss the response rate. The response rate is a measure of how much a tumor or tumor metastasis decreased in size or how much a tumor marker declined. It is easy to assume that a tumor response is equivalent to an increase in survival, but, unfortunately, it is not. In fact, tumor responses with chemotherapy for solid cancers often have no relationship whatsoever to an increase in survival. A tumor may temporarily shrink only to explode in growth a short time later. This is especially true for advanced and metastatic solid tumors.

In this example from the medical literature, five children with medulloblastoma (a type of brain tumor) responded (the tumor shrank), but as of 1979, three had already died.

Five children with recurrent medulloblastoma were treated with Vincristine, BCNU, Methotrexate and Dexamethasone. All five patients responded to therapy. Two of the patients are alive - Duffner PK, et al., Combination chemotherapy in recurrent medulloblastoma. Cancer 1979 Jan; 43(1): 41-5.

Evaluable Patients

In fact, response rates, as inaccurate as they are in telling us anything about survival in solid cancers, can be inflated by excluding some patients who died. This is known as counting evaluable patients. Patients not considered evaluable are often those who did not get the benefit of the entire treatment plan because they died while on therapy. This is an example from the medical literature.

Twenty-two consecutive patients with recurrent malignant brain tumors after radiation therapy and systemic combination chemotherapy with BCNU and vincristine, four of whom were not evaluable due to early death, were treated with etoposide. Response was observed in three of 18 (17%) evaluable patients ¦ - Tirelli U, et al., Etoposide (VP-16-213) in malignant brain tumors: a phase II study. J Clin Oncol 1984 May; 2(5): 432-7.

In the example above, the response rate was calculated after removing certain patients who died from the calculation. This obviously inflates the response rate.

Observational Bias

In addition to being a poor metric in respect to the most important measure - survival, and being subject to statistical manipulation by simply excluding patients, response rates are also subject to observational bias. For example, the following example comes from an article published by Memorial Sloan-Kettering Cancer Institute. An institutional review documents a 33% response rate. However, when the same patients are seen by the central review (doctors less vested in the success of the protocol) the response rate drops to 18%. We now understand that a response rate may lie in the eyes of the beholder.

One hundred and thirty children less than 21 years of age with newly-diagnosed high-grade astrocytoma were treated with ˜eight-drugs-in-one-day™ chemotherapy ¦ Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14 (18%) ¦ - Finlay JL, et al., Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of the 8-drugs-in-1-day regimen. A Childrens Cancer Group study, CCG-945. J Neurooncol 1994; 21(3):255-65.

Why Use This Metric?

If response rates can have little to do with survival and are subject to statistical manipulation and observational bias why are they used? One answer is because they are useful for research and publication purposes. Oncologists often want to publish papers for professional reasons. They need to report on the outcomes of their latest experiment, but if they had to wait for survival data it could take months or years until all the data was aggregated. In contrast, data on response rates can be collected quickly. Another answer is that their use was originally created in reporting the results of leukemia. In this blood cancer responses can often equate with survival. Sometimes, the more responses, the more remissions, the greater the survival. But there is a third answer why this measurement system is so widely used in solid cancers and continues in use more than 60 years after its inception. It is possible that response rates or improvement rates give oncologists the opportunity to take a more optimistic look at therapies that have limited success. Here, for example, is one of the first published uses of this metric.

A History Lesson

On March 11, 1951, Sidney Farber, MD, professor of pathology at Harvard Medical School at the Children™s Medical Center of Boston, and Scientific Director of the Children™s Cancer Research Foundation organized a conference on folic acid antagonists in the treatment of leukemia. Its proceedings were published in the medical journal Blood: The Journal of Hematology in January, 1952 (Proceedings of the Second Conference on Folic Acid Antagonists in the Treatment of Leukemia). Today, oncologists call this type of chemotherapy an antimetabolite. Antimetabolites can be thought of as wolves in sheep™s clothing. They are man-made molecules that are designed to resemble a substance that our cells need such as a vitamin or an amino acid. Once the antimetabolite enters the cell it creates damage because the cell cannot function with the counterfeit substance. The cell dies. This chemotherapy, like all traditional chemotherapy, is indiscriminate. It kills healthy cells along with cancer cells. Examples of antimetabolites currently in use include: methotrexate, fluorouracil or 5-FU, cytarabine, mercaptopurine or 6-MP, and thioguanine or 6-TG.

Farber™s antimetabolites were folic acid antagonists which meant that it was something that looked like folic acid to a cell. Folic acid is also known as vitamin B-9. Today, folic acid is suggested to be a key player in the prevention of cancer. Farber tested the antimetabolites in 238 children with various types of leukemia. The results? According to Farber, the total improvement rate in this group was 54.6%. He called this an important improvement in unselected, consecutive children with acute leukemia. He defined improvement as including complete remission, partial remission, simple clinical improvement and so on. The tables he published and the comments of his colleagues, however, are quite enlightening.

Table 5.

54.6% Improvement but Only 19% Living

This table (Table 5) comes from page 110 of the Proceedings. Please note that his 54.6% improvement rate is generated from combining 98 dead patients and only 32 living patients. (See the row titled Total Improvement.) Also, note that out of 238 patients, a total of 200 have passed away and only 38 are alive. But an improvement rate of 54.6% sounds significantly better than a survival rate of 19%. The next table is even more revealing.

Table 8.

In this table from page 111, (Table 8), Farber reports that he has 100% improvement with the drug Ninopterin. The only problem is that all those children are in the dead column. With the drug Dichloro-aminopterin, Farber depicts a 75% improvement but none of these children are living either. With Denopterin the improvement rate is 50% but all of these children are also dead. Apparently, improvement can have little to do with survival.

The thought process of Farber and his colleagues are suggested in some of the comments recorded in the Proceedings. For example, Farber is quoted as saying, One of the first important questions we would like to ask and have answered today, if possible, is this: Why are these patients, as many as 45% or 50%, who do not respond to treatment with folic acid antagonists? This is quite revealing in that Farber wonders out loud why half the patients don™t respond as opposed to perhaps a more defining question - what is the relationship between responses and improvement and survival and why have the overwhelming majority of children who responded have subsequently died?

This question becomes even more pointed when one considers that Farber also helped introduce the concept of the evaluable patient mentioned above. Farber states, If we treat all patients for three weeks, I think that we can fairly evaluate the efficacy of the compound, which takes that long, on the average, before it can be regarded as effective. Therefore, if we disregard all of those patients who died in the first day or two or three after admission to the hospital, or after the onset of therapy, and include only those treated twenty-one days or more, we find that we have 190 children, with acute leukemia, treated with folic acid antagonists since June 1, 1947. (Proceedings pages 109-110).

Table 6 on page 110 of the Proceedings reports 155 patients as dead and 35 patients as living. Also according to this table, 36.9% of the patients who were dead did not respond or improve from treatment, while 31.6% of patients who were living did not respond or improve from treatment. Therefore, of the living patients approximately 5% more patients responded to or improved from treatment. This again begs the question - what is the relationship between responses and improvement and survival and why have so many of those children that have responded also died?

The Proper Scientific Attitude

While Farber does not discuss this question or toxicity or quality of life of his patients as reported in these Proceedings, some of these issues were apparently brought forward by others in attendance.

One physician wondered why autopsies of the treated children revealed liver damage. Dr. E. Clarence Rice, Director of the Children™s Hospital of Washington D.C. stated, I would be interested in hearing others say something about the findings at postmortem examination. When we first started using folic acid antagonist therapy, we saw four children who had rather marked scarring of the liver, similar to that of cirrhosis¦ We would like to know how you interpret this. Is this an effect of the drug, or how can one account for this? (Page 114 of the Proceedings.)

Perhaps even more revealing is when one of Farber™s colleagues had a family member diagnosed with leukemia. The researcher, Dr. William Dameshek, Professor of Clinical Medicine at Tufts College Medical School did not suggest that his brother-in-law undergo chemotherapy. This is what Dameshek stated at the conference:

Still, I must confess that I continue to be pessimistic about folic acid antagonist therapy despite what has been said thus far. This was brought forcibly to mind recently when a brother-in-law of mine developed acute leukemia and we were faced with a situation as to whether or not to give him folic acid antagonist, ACTH, or cortisone. He was so sick and so obviously near to death that we decided finally to leave him alone and give him simply antibiotics and not too many transfusions, and he went on his way and died, perhaps a little more comfortably than if he had been given folic acid antagonist therapy. As we go along in our therapeutic efforts, we come to the point in some cases where we hate to inflict the so-called toxic reactions of folic acid antagonists on some of our friends, neighbors and relatives in whom this unfortunate condition may develop. I realize that this is by no means the proper scientific attitude ¦

It is striking that the doctor ended his remarks that this is by no means the proper scientific attitude ¦ Concerned with his brother-in-law™s quality of life he did not feel the administration of toxic chemotherapy was appropriate. Are science and the humane care of patients at odds? If so, where should the accommodation be made?

It deserves emphasis that chemotherapy does significantly prolong survival for some patients with blood and lymph cancers. It also deserves emphasis that Sidney Farber, MD made many significant and lasting contributions to the understanding of clinical treatments of cancers. There™s even a hospital called Dana-Farber named after him. But, it also important to understand that there is a long legacy of measuring responses and improvements and that these metrics, especially in advanced and metastatic solid cancers often have nothing to do with survival or quality of life. It is incumbent on the patient and the patient™s professional caregivers to obtain the information needed to make informed treatment decisions.


The Body of Lies About Cancer Treatments in America

Treating cancer is BIG business in America—$200 billion a year. But did you know that up to 98 percent of conventional cancer treatments FAIL miserably—and can actually make you sicker? Even worse, the powers that be are suppressing natural cancer cures that are helping tens of thousands of people get well and live cancer free—with little or no dependence on drugs, surgery and chemotherapy... and for pennies on the dollar. Enough is enough! You deserve to know the truth. Please read on...

  • WHY 9 out of 10 oncologists would refuse chemotherapy if they had cancer.
  • WHY mammograms harm ten women for every one the procedure helps.
  • WHY Big Pharma resorts to outrageous lies to convince you that their so-called "cures" work.
  • WHY thousands of Americans are saying "NO THANK YOU" to the government's new scheme to censor natural cancer remedies.
  • Plus...
  • The forbidden fruit extract that programs cancer cells to "self destruct"...
  • The powerful natural "Pac-Man enzyme" that eats cancer cells alive...
  • The natural anti-cancer vitamin banned in the U.S., but still available to you...
  • The real life miracle of one woman's escape from terminal breast cancer!    But guess what? Powerful new cancer cures like this one are being suppressed, even censored today in America—even though they could save countless lives.     Worse, many of the most highly regarded conventional cancer treatments in America are being covered-up... because of their dismal failure rates.     Why? For one reason: GREED!     Treating cancer in America is a virtual "cash cow"—$200 billion a year. And Big Pharma will do everything in it's powers to keep you dependent on its "cut, burn and poison" cancer treatments and to destroy anything that gets in the way—even if it has to bend the truth. If you think I'm exaggerating, just consider...     One of the most blatant, bold-faced cover-ups in medical history is occurring today in the treatment of cancer in the U.S. For example, be warned about...       Why? Because they know it's extremely ineffective and extremely toxic. Yet shockingly, 75 percent of cancer patients are directed to receive chemotherapy.     The truth is, a rigorous review of chemotherapy reveals it fails for 98 percent of people. And when chemotherapy was tested against no treatment, no treatment proved better. What's more, only two to four percent of cancers respond well to chemotherapy.CANCER COVER-UP No 2: Mammograms Do More Damage Than Good—and Actually HARM Ten Women for Every One It Helps!    A new study by researchers from the Nordic Cochrane Center in Demark reviewed the benefits and negative effects of seven breast cancer screening programs on 500,000 women—and the results were shocking.     For every 2,000 women who received mammograms over a 10-year period, only one would have her life prolonged, but ten would be harmed. Mammograms can actually increase a woman's risk of developing breast cancer by as much as 3 percent per year by irradiating the breast cells and triggering breast cancer.     I'm excited to report there's a new test for breast cancer with no false negatives or positives... from saliva.     That's right. Researchers from the University of Texas Health Science Center in Houston discovered that women with breast cancer carry different proteins then women with no cancer—and this can be tested by a simple saliva test—so simple a dentist can do it.       I discovered a clever trick that cancer doctors and big drug companies use to promote their cancer treatments. They use "relative" numbers to prove the effectiveness of their cancer treatments.     For instance, if you or a loved one has breast cancer, doctors may recommend the drug Tamoxifen. You'll likely hear that it reduces the chances of breast cancer recurring by 49 percent. Sounds pretty impressive, right?     But the truth is, based on absolute numbers, Tamoxifen reduces the risk of breast cancer returning by 1.6 percent—30 times less than advertised.     "Relative" numbers are used because they can be manipulated in many ways. Relative to what? It could be to a previous test or some other obscure number.CANCER COVER-UP No. 4: Drug Companies Pay Oncologists Big "Kickbacks" to Promote High-Priced, but Ineffective Cancer Drugs.      Worse, they pay oncologists kickbacks to push their drugs. For example, AstraZeneca, Inc. had to pay $280 million in civil penalties and $63 million in criminal penalties to the federal government because it paid kickbacks to doctors for promoting its prostate cancer drug.     Sad as it seems, the harassment of doctors using natural therapies to treat cancers has been going on for more than 50 years in America. Doctors treating malignant tumors with detoxification, immune stimulation, nutrient, herb and juice fasting secrets from Europe, Tibet, China and India have been persecuted and booted out of the U.S. if they wanted to continue treating cancer patients.     Take the case of William Kelly, DDS. Dr. Kelly discovered a natural enzyme therapy that, combined with strict nutrition and a detoxification regime, "digested" pancreatic cancer cells. This therapy achieved nearly a 90 percent, five-year survival rate for close to 33,000 patients—even though pancreatic cancer is by far the most rapid and deadly cancer.     According to the FTC, "Anyone mentioning a cure for cancer is automatically a quack, regardless of science backing their position." By their own admission, they state that any mention of a cancer "cure" is by itself fraudulent. And anyone using the word "cure" on a website to promote a product is instantly presumed to be guilty of criminal acts.     Censorship like this makes my blood boil! Especially with so much clinical proof, scientific findings and case studies of cancer patients being able to slow down, reverse, and even eliminate the disease from their bodies using natural means. Yours for cancer free living, Michael Cutler, M.D.
  •     What did the government do when they heard about Dr. Kelly's amazing discovery? They threw him in jail!     But now, the government is bringing out the Big Guns! The Federal Trade Commission (FTC) recently launched what they call "Operation False Cures" to stamp out natural cancer cures for good.
  • CANCER COVER-UP No. 5: The FTC Launches a Covert Campaign to Censor Natural Cancer Remedies and Financially Ruin Doctors and Companies Offering Them.  
  •     Do you know how most oncologists make money? Not by treating patients, but by selling cancer drugs.     According to the Journal of the American Medical Association, as much as 75 percent of the average oncologists' earnings come from selling chemotherapy drugs in his or her office. And at a substantial mark-up!     Americans pay the highest amount for prescription drugs in the world. Big Pharma will say it's due to research and development. But the U.S. drug industry spent over $33.5 billion in promotion costs last year.     A former drug rep from Eli Lily testified before Congress saying, "Pharmaceutical companies hire former cheerleaders and ex-models to wine and dine doctors, exaggerate drug benefits and underplay side effects."
  •    Or you may have heard through the major media that by treating early stage breast cancer, there's a 91 percent cure rate over five years. NONSENSE! You can get the same cure rate by doing nothing, as breast cancer is a very slow growing cancer.     My point is: Don't be fooled by "relative" numbers. Get the real facts, like this one: A 14-year study by two oncologists in Australia reported in the film "A Shocking Look at Cancer Studies" that treatment for all of our major cancers is totally ineffective—way below a 10 percent success rate.  
  • CANCER COVER-UP No. 3: Big Pharma Resorts to Outrageous Lies to Convince You That Their So-Called Cancer "Cures" Work—but Don't Be Fooled!
  •    The $4 billion-a-year mammogram industry urges women to rely on x-ray tests to protect their health. But what they don't tell you is mammograms are really an unnecessary and even harmful treatment.
  • CANCER COVER-UP No. 1: Up to 91 Percent of Oncologists Would REFUSE Chemotherapy If They Had Cancer.
  • Five of the Biggest Cancer "Cover-Ups" You Need to Know About!
  •     To a small group of terminal cancer patients, the discovery of cesium chloride, a naturally occurring alkaline mineral, was a ray of hope.     After all, these patients had been told to go home, make out their wills and start arranging for their funerals.     Then they discovered this remarkable mineral "starves" cancer cells... quells cancer pain in hours... extends survival rates from weeks to years... and costs just $1 a day.