Posted by: themossreports | December 11, 2010

The Procrustean Bed


Herakles killing Procrustes on his bed

Oncologists sometimes try to recruit patients into Phase I (toxicity) clinical trials. But how effective are the experimental treatments provided in such trials? In a recent 2010 study that pooled data from various phase I chemotherapy trials for sarcoma, the partial response rate was 1.6 percent (2 out of 133 subjects) and the complete response (CR) rate was 0.8 percent (1 out of 133). The median progression-free survival was 2.1 months and the median overall survival was 7.6 months. Meanwhile, 18 percent of patients experienced grade 3 or 4 (i.e., critical or life-threatening) toxicity and 12 percent dropped the trial treatment because of toxicity.

Yet here’s the amazing part. The authors of this study, at the Royal Marsden Hospital, London, concluded: “Phase I clinical trials could be considered a therapeutic option in sarcoma…due to the low risk of toxicity” (Jones RL, Olmos D, Thway K, et al. Clinical benefit of early phase clinical trial participation for advanced sarcoma patients. Cancer Chemother Pharmacol. 2010. Available at PubMed, emphasis added).

Pardon me for being blunt, but what universe do these scientists inhabit? I wonder if they themselves would submit to such toxic drugs for a less than one percent chance of a “cure” (a “cure” that in any case may last a month or so). And—it seems almost too obvious to ask—how do these scientists define a “low risk of toxicity”? Grade 4 toxicity classically includes such things as massive hemorrhages, life-threatening infection, more than ten episodes of vomiting in a 24 hour period, etc. Even grade 3 toxicity includes such things as “painful erythema, edema or ulcers and (patients) cannot eat” (http://www.rtog.org/members/toxicity/tox.html)

Sometimes I get the impression that various authors reach their conclusions first and then force their data to fit a preconceived notion. The Greeks had a term for this, a “Procrustean bed.” This term came from a myth about a highwayman named Procrustes, who physically either cut or stretched the limbs of his victims  to fit the predetermined length of his torture bed. This term has stuck for any situation in which people stretch (or minimize) the data to conform to some preconceived notion.

Advertisements

Responses

  1. Thanks, Dr. Moss. What would we do without you — and your willingness to remark on the Emperor’s clothes or lack of.

  2. If these medical researchers think that these pathetic clinical 1 toxicity trial results are a viable treatment for cancer then the western model of pharmaceutical drugs, surgery, and radiation should be “on trial” because apparently they’re no better.

  3. i recently spoke with a cancer patient who didn’t want to try an alternative method, even though she had an almost certainly fatal cancer that is almost never responsive to the standard protocol. she had heard that the alternative regimen would cause weight loss and she didn’t think that was a good idea.

    why is it that the collateral damage (hair loss, stomach lining destruction, permanent heart damage, massive nausea, memory loss, etc) of the standard protocol is considered the price that must be paid but any side effects, mild and reversible though they might be, of an alternative treatment are somehow unbearable?

    anyway, she died

  4. Once again Dr. Moss benefits us all with the actual data on the net patient value of Phase I trials. Keep in mind that since Phase II trials follow Phase I, this means that the researchers may just have determined a dose that will not as quickly kill or harm the target population. This is the point of Phase I. It does not mean that they necessarily have any significant data or justification as yet that the treatment at issue will have any actual benefit.

    Finally an outcome of Phase II trials may be considered successful if there were just tumor regression of 50% for 28 days or more. This criterion is allowed under the new perspective of the FDA that “markers” that hint at a possible usefulness may be used in lieu of actual demonstrated usefulness [e.g., the patient lived longer]. Temporary tumor regression may potentially have no net clinical benefit. So you could be enrolled in a phase III trial with little data as yet to support the notion that you may benefit. In some trials, the investigator or investigating unit [e.g., his or her Department of Oncology] may receive a signing bonus for each added patient to the trial. The point is — one should enter with open eyes and truly informed consent. One should never forget to “follow the money.”

    Just a head’s up to further the NIH mandate that all trial participants must have Informed Consent.

  5. Having PSA indicated prostate cancer for15 years and having reused all treatment other than diet, exercise and hormone treatment I have been interested to follow the “clinical trial” reports and the very short remission periods most of them obtain. What dismays, annoys and upsets me is the failure of Governments to give serious consideration the the need for voluntary euthenasia for those not only suffering, but also those about to suffer, under a painful, loss of dignity, and distressing terminal illness.

    It is time the religious and social bias against self determination was countered by common sense and support for basic humanity and dignity of the suffering and aged. There are enormous social and financial benefits to families, communities and governments by creating realistic laws to govern voluntary euthenasia for those facing the problems I outlined above. LJet’s get real!

  6. What’s the point? Science has gone balmy. I should know after over fifty years.
    Most cancers are susceptible to treatment with a phenothiazine. The story has been told in a book, In the Darker Shadow of Science. There is a simple DIY therapy on the web; enter Phenergan and energygrid into google for location.
    And if you want to see how well the work has been suppressed for decades, look at the blog above.
    i am just so sick of it all.
    Robert Jones
    PS Greetings to you, Ralph. Not my fault contact with you has lapsed.

  7. Even standard of care therapy can give some paltry results. I was offered Adrimycin for stage 2, grade 2, er+, pr weakly+, her2+ BC even though I am allergic to the mycins , congestive heart failure runs heavily in the family, and the benefits would have been 3% disease free survival over 10 years. I refused Herceptin as well thanks to Dr. Moss’ “Herceptin or Deceptin” paper. The second oncologist tried to convince me it would have given me a 55% benefit. I don’t think she realized that was relative. Thanks to Dr. Moss I knew the absolute benefit was closer to 6%. I ended up refusing all adjuvant therapy, including the AIs because of quality of life concerns and here I am almost 5 years later, only suffering from quality of life issues related to surgery, as opposed to that of adjuvant therapy, as well. I think it is time that the medical community give the same sway to “quality of life” that they give to “quantity of life”!

  8. Is there a link to the actual study Dr Moss?

  9. Your article makes me think of some of the medical atrocities of the past:

    Blood letting, leeches, purgatives, emetics, lobotomies, electroshock, resistance to the germ theory and hand washing, eugenics, …. chemotherapy ….

    It probably just comes down to doctors who do not want to change very lucrative life styles and drug companies who work with them to generate huge profits for their employees and stock holders and for the doctors themselves.

    Cancer patients are not good advocates because they either die or try to forget cancer if they survive.

    Sometimes surviving parents and relatives can be effective advocates but there are not enough to be effective.

    Since America has definitively transformed itself into a plutocracy, even majorities have little power. For example, in late 2009, 57% of Americans were against the Afghanistan war: http://politicalticker.blogs.cnn.com/2009/09/01/cnn-poll-afghanistan-war-opposition-at-all-time-high/

    Politicians, who are elected by multinational corporations, don’t care. They just continue to do the bidding of their masters.

    Many thanks, Ralph. You and many other unsung heroes help us keep the faith.

    May each of us move the ball forward in our own way, using the resources at our disposal.

  10. Please help if u can. Diagnosed with mucinous adenocarcinoma in march 09 of the appendix. Sent to Mayo clinic and had a rt hemicolectomy w/removal of 27 lymph nodes–all clear. Refused their chemo. 6 months later, tumors showed up on CT in abdomen as possible PMP. Saw a specialist in San Diego who did exploratory lap and then suggested cytoreductive surgery with HIPEC. Had that 4 wks ago and pathology showed a high grade appendix cancer. Not PMP. How can this be? Now they want me to start systemic chemo, which i always said i wouldn’t do. I don’t know what to do. I am 42 years old with 3 young kids ages 11,9, and 5. Please email any suggestions at rachael.underwood@shctc.k12.oh.us

  11. my admiration and gratefulness is infinite for Dr. Moss.
    his work amazes me. and may have save or improve my
    quality of life.
    Thank you, Dr. Moss.

  12. my admiration and gratitude is infinite for Dr. Moss.
    his work amazes me. and may have save or improve my
    quality of life.
    Thank you, Dr. Moss.

  13. We need to understand exactlly what phase 1 trials are. Once cell culture and animal studies have shown that a specific treatment has an effect, then a phase 1 study in humans is performed to work out the maximum dose of a drug that can be given without severe toxic side effects. Therefore the amount of toxicity shown in these phase 1 trials is not surprising. However, what is sad is the lack of efficacy shown in these trials although officially they are not designed to show efficacy.
    The fact of life is that chemotherapy is generally ineffective as a cure except for testicular tumours and choriocarcinomas and as an adjuvant treatment in breast and colon tumours which have been surgically excised.
    The bottom line is we need more trials looking at therapies such as Coleys fluid and intravenous or liposomal vitamin C which are non toxic and the former has a proven history of an anti-cancer effect which is equal or superior to modern chemotherapy. However, these are not patentable and therefore the pharmaceutical companies are not interested as they won’t make any money.


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Categories

%d bloggers like this: