Drug Repurposing for Advanced PC 1. Metformin

I was asked to reply as one of the authors of one of the studies above
(the Mayo and Vanderbilt study, in which we saw that metformin reduced
cancer rates for many types of cancer compared to other diabetic
medications and when compared to non-diabetics). The post above is an
excellent summary. You will notice that most of the studies performed so
far use retrospective reviews, and they define cancer patients, diabetes,
and exposures to metformin in different ways. Also, they have different
study sizes, and some of the studies that don't show a benefit may be
underpowered to show an effect.

As a general internist (not an oncologist), my take on the field is that
if you have diabetes and cancer, one should consider with their doctor if
metformin makes sense as part of a antidiabetic regimen. I am not aware
of solid data to suggest to use of metformin for non-diabetics, since metformin
can itself cause risk because it lowers your blood sugar, which certainly
can be harmful.

Dr. Denny,

Thanks for your reply, and for the study you did. I think you are on the forefront of two important new trends in medicine. Drug repurposing has the potential to vastly change the trajectory of health care costs. With new drugs costing upwards of $2B for development and testing, and a very lengthy approval process, it pays to look at what we already have in our armamentarium. Last month, the 3rd Annual Drug Repositioning, Repurposing, and Rescue Conference was held in Boston. Patient advocates on this site may notice that one of the stated themes this year was "Emphasis on and engagement with patient advocacy groups, who are investing in drug repositioning efforts to an unprecedented degree."

The other interesting trend you evidenced is the rising use of electronic health record data mining. Because the government has provided incentives, establishing standards for this, and setting universal requirements for it over time, this has the potential to vastly increase our medical knowledge. However, Big Data is useless without the pioneering efforts of researchers like you who are able to extract meaningful information from it.

Tony, my question for clinicians is whether they are using them in their practice off label, and what kind of results they are seeing; e.g., a slowing in PSADT or other measure of progression. I know, for example, that Dr. Scholz is prescribing metformin (and several others) off label for non-diabetic men. The point of repurposing is that we don't have to wait for clinical trials. With some drugs, like metformin, statins, and Celebrex, for example, the risk is low and manageable, so clinicians are already using them.

I don't know that your guess that very few are prescribing it outside of trials is true. In fact, based on anecdotal evidence from my support groups, it seems to be widely prescribed.

The Xu study actually did look at prostate cancer specifically and breaks out the data separately for that subgroup. The large mortality reduction I showed here was for prostate cancer patients. Their call is for validation studies using electronic health record data at other institutions (They looked at Vanderbilt and Mayo). This kind of research is at the forefront of investigation because of the new Federal laws being phased in and already in place in many large institutions, and the comparatively low cost of such studies compared to RCTs. The use of Big Data will become increasingly important to medicine.

I titled these threads "for advanced PC" because that is the group most interested in such adjuvant therapies, and the evidence I gave has relevance to them. I know that Scholz gives it to high risk patients. I assume Myers does as well, since he prescribes drugs with much inferior safety records to his patients. Compliance would not be much of an issue for this group, as the GI SEs are manageable.

If there were prospective data from randomized clinical trials there would be no need to prescribe any of these drugs off label - for some, the manufacturer could extend his patent by applying for and getting FDA approval to market them for the new use. For the drugs that are already generic, there is, as you say, no incentive to finance clinical trials, and with NIH cutbacks, they will rarely get financing. The point of these posts is that these drugs are or may be used legally off label, (1) now, without waiting, and (2)without adding the enormous cost (or the convincing data) of a long term RCT. For advanced cancer patients, metformin offers enormous potential benefit with very little risk.