Re: Ralph Moss: The Procrustean Bed

[Guest guest]

Typically, phase I studies require for eligibility relapsed/refractory cancer

where the standard protocols are no longer effective. Here the expected

toxicities from the experimental agent can be less than the risks of the disease

untreated, or treated with standard therapy.

Increasingly, targeted therapies offer science-based hope that the

investigational approach can be effective and less toxic (not to be confused

with non-toxic) by binding a target in the cells involved in the malignant

process, including pathways involved in treatment resistance. ... So for my

money, in this context, participating in a trial - even a dose-finding trial -

can be a reasonable treatment decision, particularly if the participants can

receive the dose found to be optimal ... active with acceptable toxicity.

Is Dr. Moss (not a medical doctor) suggesting that alternative medicine is a

better approach in this context? If so, which and for what type of cancer - and

what evidence is he providing to make the case?

Is his goal to improve the clinical research system?

If so, he must be more specific. What drug, what diagnosis, what eligibility,

what is the natural history ... what are the competing studies? Lacking that,

this seems typical unproductive propaganda to foster general mistrust of

clinical rsearch, which we all depend on for progress.

Karl

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> 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.

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> 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 "

( 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).

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> 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)

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> 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.

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> --Ralph W. Moss, PhD

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