Dean's World

Defending the liberal tradition in history, science, and philosophy.

"Do Not Listen To What They Say -- Go See" (Chinese Proverb)

by George L Gabor Miklos PhD and Phillip John Baird MD PhD

Patients rarely die from a primary tumor

Problems arise when a cancer spreads (metastasizes) to another part of the body and destroys a vital organ (20-23). In breast cancer, it is not the lump that is the killer, it is the cells that leave that lump and spread to the brain and bones, for example, eventually replacing a vital organ with tumor tissue. Ninety percent of the deaths from cancer are due to the spread of these maverick cells that develop the capacity to leave home and embark on a journey throughout the body. If a primary tumor is diagnosed before any of its cells have left and the tumor is surgically removed, the patient is completely cured. This is the only cure that exists; removal of a primary tumor before any of its cells have moved to other parts of the body.

Facts and figures from the American Cancer Society

An estimated 560,000 US citizens will die from cancer in 2007 (www.cancer.org). The five largest categories of deaths will be; lung cancer, (160,000), colorectal (53,000), breast (41,000), pancreas (33,000) and prostate (27,000). Most cancers will occur in individuals 55 years or older. Deaths from childhood cancers, between the ages of 0 and 14, are relatively rare, estimated to be 1,500.

Facts and figures from the National Cancer Institute

The latest figures from the NCI’s publicly accessible databases reveal the relative 5 year survival of patients with various metastatic cancers over the 30 year period, 1973 to 2004 (seer.cancer.gov):

survival with metastatic breast cancer improved from 19 to 23 percent.
survival with metastatic colorectal cancer improved from 6 to 9 percent.
survival with metastatic prostate cancer improved from 28 to 34 percent.
survival with metastatic lung cancer improved from 1 to 2 percent.

(Editor's note: these figures gathered over more than three decades amount to this: they can claim a "100% improvement" on lung cancer by improving survivability from 1% to 2%, and "a 50% increase in survival from colorectal cancer" breathlessly in press reports when they went from 6 to 9% improvement. This after multiple decades and tens of billions of dollars. That's how the gullible press, government-paid bureaucrats, and corporate spin-doctors actually express things. --Dean)

The improvements in survival are less than 0.2 percent per year, a miniscule change. Dr Jane Weeks, an oncologist at the Dana-Farber Cancer Center provides clinical candour; A surprisingly high proportion of patients with metastatic solid tumors don’t realize that there is no chance for cure. I’ve wondered how many patients in exactly that situation have been shocked to learn otherwise from the coverage about Elizabeth Edwards (17).

The truth is that all metastatic cancers are incurable despite the enormous sums of money poured into research and drug development, as well as the large amounts of chemotherapy, radiation and new drugs that have been poured into patients (24,25).

Some patients do respond to blockbuster drugs. Increased survival times, however, are of the order of months, not years. Side effects are common and the quality of life is dreadful. Approximately ten percent of breast cancer patients who receive Herceptin, for example, develop cardiac toxicity, while another thirty percent develop metastases to the brain (26).

Different cancers respond differently to chemotherapy and radiation

There are hundreds of different types of cancer that have been carefully classified by pathologists (www.afip.org). Each differs in its aggressiveness to spread and its resistance to drugs.

A common misconception is that if one type of cancer can be cured, so can all others. The case of Lance Armstrong, who was cured of testicular cancer, is believed to be generalizable to other cancers. However, cancer is a variety of types. Thus testicular cancer encompasses seminoma, embryonal carcinoma, teratoma and choriocarcinoma. Seminomas are generally slow growing, whereas non-seminomas tend to spread more quickly. Grade 1 seminomas are sensitive to both chemotherapy and radiation therapy and if detected early enough and treated, over ninety percent of patients are alive after 5 years and hence are considered to be cured (27).

In contrast, other cancers, such as colorectal cancer, pancreatic cancer and melanomas of the skin are intrinsically resistant to radiation and chemotherapy. Less than five percent of patients with pancreatic cancer are alive after five years.

Blockbuster drugs

The effectiveness of anticancer drugs is measured in two major ways. The most accurate is Median Overall Survival, the time by which half the patients have died from disease. The other is Progression-Free Survival, which essentially measures how long after drug treatment the cancer begins to grow again. This is a subjective measurement since it involves estimating tumor size by scans. Given these two methods, how do the various drugs perform?

THE CHICAGO DRUG SHOW

The annual meeting of the American Society for Clinical Oncology is the premier forum in which upcoming cancer treatments are presented. It is the cancer equivalent of the Detroit Auto show. New drugs are exhibited by all the pharmaceutical firms and media and stock market analysts report on the upcoming drug pipeline. This year’s meeting was attended by 30,000 oncologists, researchers and drug and biotechnology company representatives. What progress emerged on cancer cures?

The 2007 progress report

Nexavar: Onyx Pharmaceuticals and Bayer HealthCare Pharmaceuticals reported on a new use for their drug Nexavar. In combination with chemotherapy, Nexavar boosted median overall survival of liver cancer patients by 2.8 months. This improvement was described in Forbes as a breakthrough liver cancer treatment (14) and by Dr Llovet of the Mount Sinai School of Medicine in New York city as "a new reference standard for systemic therapy of liver cancer patients after thirty years of research and more than 100 randomized controlled trials performed" (14). Surely after thirty years, innumerable clinical trials, billions of dollars invested and an increased median survival time of 2.8 months, the use of the word "breakthrough" is absurd.

Axitinib: Pfizer reported that their drug Axitinib plus chemotherapy for advanced pancreatic cancer boosted median overall survival by 1.3 months compared to chemotherapy alone. When used for metastatic breast cancer, Axitinib plus chemotherapy boosted progression-free survival by 1.2 months compared to chemotherapy alone. However, along with this extra 5 weeks of life, there were common adverse events such as nausea, fatigue, proteinuria, stomatitis/mucositis, hypertension, diarrhea and neutropenia. Further risks are documented in Pfizers Annual Report Forms, 10-K, 10-Q and 8-K.

Erbitux. ImClone Systems and Bristol-Myers Squibb provided data on Erbitux for head and neck cancer, the results being highlighted in BusinessWeek. Erbitux plus a chemotherapeutic regimen boosted median overall survival for head and neck cancer patients by 2.7 months compared to chemotherapy alone.

Avastin. The Wall Street Journal reported on data released by Genentech on the drug Avastin (28). Avastin plus interferon boosted progression-free survival for kidney cancer by 4.8 months compared to interferon alone. In addition, Avastin plus a chemotherapeutic regimen for advanced forms of lung cancer boosted median progression-free survival by 6 weeks compared to chemotherapy alone.

Herceptin. The New York Times reported on concerns with the allocation of patients to receive Herceptin, which is held to be the paragon of personalized medicine in breast cancer (29).

Women with breast cancer are classified into two groups on the basis of molecular tests involving a gene called HER2. The groups are termed HER2-positive and HER2-negative. Only HER2-positive patients usually receive Herceptin, as the drug is thought to have little benefit for the HER2-negative group. However, it was reported that some women experienced a benefit irrespective of their HER2 status, indicating that Herceptin may be being incorrectly targeted to these two groups (29).

These findings left some doctors incredulous and confused as to what treatments to now apply to their breast cancer patients. "Here we are, 10 years into it and we don’t know how to test for it," said Dr Marc Citron, an oncologist from Lake Success, New York (29).

The main message to emerge from this prestigious forum is that specific drugs in combination with chemotherapeutic regimens do extend median survival for a period varying from weeks to months. However, these figures apply to a population of patients, not to an individual. One patient may survive for years, whereas another is gone after a few weeks. Currently there is no accurate way by which a doctor can predict an outcome for a particular patient.

(Next up: "The cancer cells that leave home have extra DNA capabilities." --Dean)

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Scott Kirwin (mail) (www):
Interesting.
Last night I read this article about cancer in the July issue of Scientific American. Current thinking about the disease as being "rogue cells" suffering DNA damage is changing towards tumor-as-organ model, whereby the tumor has a support network that includes hijacking the immune system.

The goal is to make cancer a chronic disease that doesn't kill you, but you live with until you die from something else.
7.31.2007 10:23am
TallDave (mail) (www):
Treating cancer with drugs is like weeding your lawn with napalm. It's criminal that we're spending such a large proportion of available resources on treatments of such infinitesimal effectiveness, rather than doing the basic research necessary for real cures.

In 20 years, we should be able to do protein modelling sufficiently well that we can infect cancer patients with viruses that kill only cancers, based on the cancer's unique properties.
7.31.2007 4:12pm
maggie may - labrat:
This is all interesting data - but as someone who's worked in healthcare for a long time - I don't think it's fair to portray the whole industry as an abysmal failure.

Cancer care has vastly improved over the past 5-10 years from what I see. If nothing else we are not killing them with chemo as much as we used to.

We may not have a cure for metastatic cancer yet, but our treatments are definitely giving patients more time with a better quality of life than we used to.
7.31.2007 5:56pm
Hank Barnes (mail) (www):
This is great stuff, Dean!

For folks interested in this, one of the better articles on the quest to find the cause of cancer was published in SciAm about 4 years ago-- Untangling the Roots of Cancer by Wayt Gibbs.

The recent follow-up to the Gibbs piece in SciAm -- Chromosomal Chaos, was, of course, written by our favorite scientist, Dr. Peter Duesberg.

BTW, TallDave's analogy -- weeding your lawn with napalm -- is exactly right. Poison (chemo), Slash (surgery) and Burn (radiation) have been hyped and exaggerated as effective treatments.

Barnes, Hank
8.1.2007 12:03am
Eric M (mail) (www):
My cousin's wife has been diagnosed cancer free (from melanoma) after a regiment of MDX-010 (still in trials). Any thoughts on the applicability of this sort of drug to other forms of cancer? I did some reading about it a while ago and it seemed like a distinct break from the chemo approach.
8.1.2007 1:46am
Dean Esmay:
Eric, I hate to try to field questions like yours before the entire series is done, and I'll let Drs. Miklos and Baird answer commenters after the series is done some time next week.

However, on a personal level, I'll say a few things:

1) I'm actually in favor of FDA "fast track" testing of various approaches--in fact I think we should be testing far more approaches than we are now and the "fast track" system is actually much too slow and limited.

2) On a more personal level, I am deeply skeptical of any approach which looks at viruses and vaccines as a primary preventive or treatment for malignant cancer of most sorts. That someone got better after being part of some experiment really doesn't prove much of anything, which is the whole purpose of rigorous application of the scientific method in the first place.

I know that's not an entirely satisfactory answer. And it's only my personal opinion. Miklos and Baird can answer if they want to but all I'll say is: "well yes, that's interesting that someone with melanoma got better when getting this vaccine. Others with melanoma also get better without this vaccine. So what is the significance?"

To some that seems evasive. To others it seems dry and clinical. In fact it is the truth.

But on a personal level? I think the idea that a virus causes most (most) cancers is probably bullshit on its face.
8.2.2007 8:41pm
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