The dandelion phenomenon

This post turned out to be way too long, so I decided, as I have done with a few other posts that got out of hand (!), to divide it into two parts. I will post the second, longer "chapter" tomorrow.

Yesterday I read, and was spellbound by, a study on stem cells conducted by Dr. Matsui et al, and published in “Blood” in September 2005. The full study is available online: An extraordinary study that makes some interesting points concerning “current methodologies used to develop new cancer therapies.” I thought I would highlight some of them (conventional methodologies only are discussed, by the way), even though you can go read the full text for yourselves: it’s easy to read, unlike most scientific texts. A real pleasure!

The abstract starts out with the following statement: “Although most cancer patients respond to therapy, few are cured. Moreover, objective clinical responses to treatment often do not even translate into substantial improvements in overall survival.” As various studies have shown, they write, the response of myeloma patients to chemotherapy does not lengthen their survival. An explanation for this could lie in the cancerous stem cells: “a rare population of cells that exclusively maintain the ability to self-renew and sustain the tumor.”

Now let’s have a look at the full study. The researchers immediately take a strong stance on the issue of "clinical response": “More than 30 new anti-cancer drugs have been approved over the past two decades. Approval required all of these drugs to show a clinical benefit, which can be documented by objective measurements of tumor response, improvements in quality of life as assessed by questionnaires, or a delay in the time to recurrence. However, these benefits have led to only modest increments in survival for the majority of cancer patients. Emerging laboratory and clinical data are beginning to point out potential flaws in the current methodologies used to develop new cancer therapies.”

What happens today is that when patients respond to a drug in a clinical trial, that drug is developed and made available as quickly as possible, with the idea that it will have an impact on the patients’ survival. If clinical trial designers, however, had to take into account “recurrence or an improvement in overall survival,” they would have to deal with very complex issues, such as large numbers of patients and allowing enough time, probably a lot of time, for follow-up.

The researchers do add that “objective responses” to chemotherapy may decrease side effects and improve quality of life. The issue at hand, though, is survival, for which “there is surprisingly little evidence.” As far as multiple myeloma is concerned, for instance, “neither the magnitude nor the kinetics of clinical response has an impact on survival.”

The researchers strongly criticize the concept of complete remission: “In actuality, the major rationale for the use of objective clinical response as a surrogate for biologic activity is the premise that a complete remission must precede cure.” They declare instead that “a complete remission by standard criteria may be neither a prerequisite nor a requirement for the actual generation of a cure.” This will become clearer as we proceed through the text.

Before signing off, I would like to urge everyone to read Earl’s story, in case you haven’t already done so (Beth posted his story on her blog, and I posted about her…post in early January). See his comment on my January 25th post. Have a great Sunday!

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