The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 13 No. 3 • June 2010

Experimental Treatment That May Never Be Approved by the FDA

Dichloroacetate (DCA) is an analog of acetic acid in which chlorine atoms replace two of the three hydrogen atoms on the methyl group.1 It has interesting metabolic effects. DCA interferes with glycolysis, an inefficient ATP generating pathway that is relied upon by most cancer cells for their energy needs. By inhibiting the mitochondrial enzyme pyruvate dehydrogenase kinase, DCA alters carbohydrate metabolism so that cells have to increase energy production by oxidative phosphorylation rather than glycolysis. This eliminates advantages that glycolytic metabolism provides to cancer cells; for example, glycolytic enzymes are reported to have direct antiapoptotic (reducing programmed cell death) actions, lactic acid produced by glycolysis promotes angiogenesis and interstitial matrix breakdown (hence, promoting metastasis) and decreased mitochondrial glucose oxidation is associated with inhibition of mitochondria-dependent apoptosis.2 DCA had already been tested for treatment of lactic acidosis in humans and seemed to be relatively safe.3,4 A recent study of five patients with glioblastoma multiforme (a devastating form of brain cancer, in which patients usually live no more than a year after diagnosis) showed beneficial effects with DCA treatment.2 “All except patient 3 were clinically stable at month 15 of DCA therapy and alive at month 18 (telephone follow-up).”2 The same authors had previously published a study showing DCA treatment in rats with human tumors shrunk the tumors.

Unfortunately, DCA is not approved for the treatment of cancer in the U.S. and, worse yet, the drug is off patent and is therefore an “orphan.” Nobody is likely to be willing to spend the hundreds of millions of dollars on large clinical trials that would be required by the FDA for approval to treat glioma. Hence, there is a fair amount of activity among glioma patients (as reported in various web sites) to get and use the drug without waiting for approval.5 Needless to say, there is considerable controversy surrounding this “self-approval” by patients, even including the lead author of paper #2, who worries that people are not only placing themselves in danger, they may also be jeopardising the conduction of clinical trials that would determine whether the drug actually works. We disagree with this attitude entirely. A drug approval process that requires dying people to simply roll over and die rather than to seek out and try a potential (even risky) treatment is a drug approval process that needs to be given the boot. Whose life is it, anyway? In fact, it would be hard to respect somebody who didn’t make an effort (not necessarily by taking DCA) to save his own life.

Researchers will, in our opinion, still be able to recruit subjects to participate in clinical trials by providing extra value to patients in the form of tests to evaluate ongoing effectiveness and to catch early signs of toxicity that a patient might not notice on his own. In the case of glioma, you still have the problem in the usual design for a clinical trial of requiring people to take a chance on getting a placebo or “standard care” (a death sentence) to compare with the outcome of experimental treatments. We would advocate instead using “historical controls” for such comparisons, thus allowing all subjects the opportunity to try (for better or for worse) an experimental therapy and to do so at three different dosage levels.

That brings up the question of what alternatives to the current regulatory approach to off-patent drugs discovered to have new uses might be appropriate. An editorial in the 20 May 2010 Nature suggested that perhaps the “government” (with your money) could pay for clinical trials (terrible idea) or that, as the editorial says it is done in Europe, add an extra year of patent exclusivity if new uses are found for an off-patent previously approved drug (this would be ineffective, as a year is unlikely to allow recovery of the immense costs for clinical trials). What we suggest is that, once a drug has been approved for safety, any new uses should be considered matters between patients and doctors without any need for FDA approval. Of course, we believe it should be understood that in the use of drugs for unapproved uses, the patient takes his chances with his own life and the doctor takes his chances with his reputation and conscience with no liability for the drug manufacturer (except for defective products that cause injury).


  1. Linda Geddes. Cancer therapy: When all else fails. (28 March 2007).
  2. Michelakis et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med 2:31ra34 (2010) DOI: 10.1126/scitranslmed.3000677.
  3. Stacpoole et al. Treatment of lactic acidosis with dichloroacetate. N Engl J Med 309(7):390-6 (1983).
  4. Curry. Lactate-lowering effect of dichloroacetic acid: a model for investigation of anxiolytic drugs? Psychopharmacol Bull 25(2):202-3 (1989).
  5. Helen Pearson. Cancer patients opt for unapproved drug. Nature 446(7135):474-5 (29 March 2007). Two websites are mentioned in this 2007 article: (still there as of June 15, 2010) and (access forbidden as of June 15, 2010); of course, the two of us cannot vouch for ANYTHING said or sold at these websites.)

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