The Promise of the Combination of Adriamycin and Carnitine For the Treatment of Cancer

October 23, 2002

By Stephen L. DeFelice M.D.

During the Vietnam war, Major James Vick, an expert cardiovascular pharmacologist, and I were stationed at the Walter Reed Army Institute of Research (WRAIR) where we conducted animal studies which showed that carnitine dramatically reversed myocardial ischemia lack of oxygen to the heart.

Carnitine is a naturally occurring substance that transports fatty acids into mitochondria, the furnace of the cell, where they are metabolize to produce ATP or energy. It is present in high concentrations in high energy-requiring cells such as those found in the heart as well as sperm cells. We postulated that carnitine works by maintaining the function of the mitochondria preventing cellular death, or apoptosis, which commonly follows ischemic attacks.

At that time, we were also interested in the toxicity of adriamycin, an anti-cancer drug, that is highly effective in various types of malignancies.

Though it is extremely effective in killing cancer cells, its dose, unfortunately, is significantly limited because of cardiotoxicity that can lead to fatal heart failure.

Major Vick and I wondered whether carnitine could eliminate or at least reduce adriamycin’s cardiac toxicity. If so, then higher doses could be given to cancer patients increasing its tumor-kill capacity resulting in the saving or prolonging of many more lives.

We initiated a series of acute and chronic animal studies ranging from isolated dog hearts to intact monkeys. In every laboratory model carnitine dramatically reduced adriamycin’s cardiac toxicity!

We also studied the effect of carnitine on daunomycin, a derivative of adriamycin, which has similar anti-tumor activity and cardiotoxicity. Carnitine worked equally as well.

It is important to note that other investigators have subsequently confirmed our findings for both substances.

During our initial excitement a sobering- and discouraging, may I add- thought occurred to us. What if carnitine also blocked adriamycin’s anti-tumor activity?

We then collaborated with a cancer research specialist and colleague, Dr. Steve Barranco, to plan a laboratory study that would test this possibility.

The study, using exponentially growing mono layered cultures of Chinese hamster ovary cells, showed that carnitine did not block adriamycin’s cell kill capacity but actually increased it by a factor of ten! (1) Other investigators also have confirmed that carnitine does not block the anti-tumor activity of adriamycin. (2)

After our discovery, we popped open a bottle of champagne and a can of peanuts to celebrate this potential medical breakthrough for cancer patients.

But the celebration was short-lived. For over thirty years I have, as an individual, have tried to find a company or organization to sponsor a clinical trial to determine whether this promise would hold in certain cancer patients.

I’ve failed. Despite an intensive personal effort there was, and remains, little interest.

I then made available $50,000 of my own money as an grant for the medical institution that would conduct a preliminary clinical study to evaluate the promise of the combination in a small number of certain cancer patients.

It was not enough! The medical institutions all requested that I indemnify them because of the fear that carnitine might not block cardiac toxicity and the probability of being sued would be high. The cost for the amount of indemnification left little funding for the clinical trial costs.

If Congress had passed the Physician Volunteer (Doctornaut) Act that I proposed thirty years ago which would permit physician patients to volunteer for clinical studies at much reduced costs and risks, our hypothesis would have been tested a long time ago.(3) If confirmed, it is likely that hundreds of thousands of cancer patients — and perhaps more — who have succumbed to their neoplastic diseases would be with us today. (3)

1. Vick: J.A., DeFelice: S. and Barranco: S. Potentiation of the Cytotoxicity of Adriamycin by the Cardioprotective Drug Carnitine. Cancer Research 8: 312, 1978
2. Alberts: D.S., Peng: Y.M., Moon: T.E., and Bressler: R. Carnitine Prevention of Adriamycin Toxicity in Mice. Biomedicine Nov; 29(8): 265-8
3. DeFelice Commentary: Doctornauts, Physician Volunteers for Clinical Research: The Time Has Come for Congress to Act.