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Highlights

The Carnitine-Doxorubicin Promise For the Treatment of Ovarian Cancer

Brief History

What is carnitine? Carnitine is a naturally occurring substance found in most human cells. Its main action is to transport fatty acids across mitochondrial membranes where they are metabolized to produce energy or ATP. It also has other actions. It is found in high concentrations in high energy requiring tissues such as cardiac, skeletal muscle and sperm tail.

FDA status: It is FDA approved as an Orphan Drug for the treatment of Carnitine Deficiency and for patients on renal dialysis. Regarding safety, in clinical studies both with the intravenous and oral forms it has been found to be devoid of significant toxicity as evidence in the package insert. In certain international countries, it has been approved for cardiovascular indications such as myocardial ischemia and congestive heart failure.

Carnitine’s cancer cell killing or apoptosis properties other than ovarian experimental cancer models: Carnitine has apoptotic tumor size reduction or positive surrogate marker anti-cancer activity in a number of models including hepatic and colon neoplasms. Carnitine’s relatives, acetylcarnitine and proprionyl carnitine, which are largely converted to carnitine, have also demonstrated anti-cancer activity when given with chemotherapeutic agents. For example, acetylcarnitine eliminates mitoxantrone resistance in leukemic mice and proprionylcarnitine, when administered with taxol, enhances tumor kill capacity of murine breast cancer cells. It is important to note that the results of studies on the anti-cancer properties of carnitine are not consistently positive depending on the model used.

Carnitine and doxorubicin activity in non- cancerous and cancerous ovarian culture cells: In Chinese hamster ovarian culture cells carnitine increases doxorubicin’s cell kill capacity by tenfold. In human ovarian cancer culture cells, which is a model predictive of doxorubicin’s clinical effectiveness in patients with ovarian cancer, as expected, demonstrated its apoptotic activity. Carnitine, however, killed over 50% of these cells as well as added to doxorubicin’s apoptotic effect.

Carnitine’s broad anti-toxin properties: In laboratory studies carnitine consistently prevented or reversed toxic effects of numerous substances, including E.coli toxin and snake venom. It did the same with chemotherapeutic drugs such as bleomycin and carboplatinum.

Carnitine blocks doxorubicin cardiac toxicity: In dozens of acute and chronic animal studies, including monkeys, carnitine either prevented or reversed cardiac toxicity.

The conclusion: the combination of these two drugs may both increase tumor kill capacity in patients with ovarian cancer and also reduce cardiac toxicity.

The clinical study in patients in Stages III – IV ovarian cancer: A study has begun in patients who are taxane-platinum resistant in a Northern New Jersey hospital. IRB approval will soon be requested at another close by hospital. We are seeking patient volunteers to participate in the study. If there is interest, the patient’s physician should contact Patricia Park at 908 272 1600 or send an email to fimdefelice@aol.com.

Stephen L. DeFelice, M.D.

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