MELATONIN: May benefit ovarian cancer, and reduce chemotherapy side effects as well.

The Foundation's Chemotherapy Protocols have been revised to reflect new findings. These protocols provide concise information about reducing the side effects of cytotoxic chemotherapy, and using other drugs to synergistically enhance the cancer-cell killing effects of chemotherapy.

There are nutrient and hormone therapies that can mitigate the toxicity brought about by cancer chemotherapy. In peer-reviewed scientific papers, nutrients such as coenzyme Q10 and vitamin E have been shown to protect against chemotherapy-induced cardiomyopathies. Melatonin has been shown to protect against chemotherapy-induced immune depression.

One study specifically suggested that cancer patients treated with Adriamycin, a toxic chemotherapy drug, should supplement with vitamins A, E and selenium to reduce its side effects.

Another study showed that the antioxidants vitamin C, vitamin E and N-acetylcysteine could protect against heart muscle toxicity when cancer patients are receiving high doses of chemotherapy and/or radiation therapy. This study documented that no chemotherapy patient in the antioxidant group showed a fall in the left ventricular ejection fraction, compared with 46 percent of the patients not receiving antioxidants. Further, no antioxidant-treated patient showed a significant fall in overall ejection fraction, while 29 percent in the group not getting the antioxidants showed a reduction.

In the radiation therapy group, left ventricular ejection fraction did not change in patients treated with antioxidants, but 66 percent of patients in the group not receiving the antioxidants showed a fall in ejection fraction.

Experimental data have suggested that the pineal hormone melatonin may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, melatonin has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy.

A study was performed to evaluate the influence of melatonin on chemotherapy toxicity. Patients randomly received chemotherapy alone or chemotherapy plus melatonin (20 mg a day in the evening). Thrombocytopenia, a decrease in the number of blood platelets, was significantly less frequent in patients treated with melatonin. Malaise and lack of strength also were significantly less frequent in patients receiving melatonin. Finally, stomatitis (inflammation of the mouth area) and neuropathy were less frequent in the melatonin group. Alopecia and vomiting were not influenced.

This pilot study seems to suggest that administration of melatonin during chemotherapy may prevent some chemotherapy-induced side effects, particularly myelosuppression and neuropathy.

Expensive drugs like Neupogen (granulocyte-colony stimulating factor-GC-SF), granulocyte macrophage colony stimulating factor-GM-CSF and interferon-alpha (an immune modulating cytokine) can restore immune function debilitated by toxic cancer-chemotherapy drugs. If you are on chemotherapy, and your blood tests show immune suppression, you should demand from your medical oncologist the appropriate immune restoration drug(s).

Studies have shown that melatonin specifically exerts colony stimulating activity and rescues bone marrow cells from apoptosis (programmed cell death) induced by cancer chemotherapy compounds. Melatonin has been reported to "rescue" bone marrow cells from cancer chemotherapy-induced death. The number of granulocyte-macrophage colony-forming units has been shown to be higher in presence of melatonin.

In addition, melatonin has been seen to amplify interleukin-2's anti-cancer action and to reduce its toxicity. Melatonin use in association with interleukin-2 cancer immunotherapy has been shown to have the following actions:

- Amplifies interleukin-2 biological activity by enhancing lymphocyte response and by antagonizing macrophage-mediated suppressive events;

- Inhibits production of tumor growth factors, which stimulate cancer cell proliferation by counteracting lymphocyte-mediated tumor cell destruction; and

- Maintains a circadian rhythm, which often is altered in human neoplasms and influenced by cytokine exogenous injection.

The dose of subcutaneous low-dose interleukin-2 (3 million IU a day) and pharmacological doses of melatonin (40 mg a day orally) in the evening have appeared to be effective in tumors resistant either to interleukin-2 alone or to chemotherapy. At present, 230 patients with advanced solid tumors and life expectancy less than six months have been treated with this melatonin/interleukin-2 combination. Objective tumor regressions were seen in 44 patients (18 percent), mainly in patients with lung cancer, hepatocarcinoma, cancer of the pancreas, gastric cancer and colon cancer. A survival longer than one year was achieved in 41 percent of the patients. The preliminary data show that melatonin synergizes with tumor necrosis factor (TNF) and interferon-alpha by reducing their toxicity.

Drugs to mitigate chemotherapy-induced nausea include Megace and Zofran. The high cost of Zofran has kept many cancer patients not covered by insurance from obtaining this potentially beneficial drug. If you are receiving chemotherapy and are suffering from nausea, you should be able to demand that any HMO, PPO or insurance carrier pay for this drug. Zofran can enable a cancer patient to tolerate chemotherapy long enough for it to be possibly effective.

One study evaluated glutathione, vitamin C and E for their anti-vomiting activity. Cisplatin-induced vomiting in dogs was significantly reduced by glutathione, vitamin C and E. The anti-vomiting activity of antioxidants was attributed to their ability to react with free radicals generated by cisplatin.

The Life Extension Foundation introduced the world to melatonin in 1992. And it was the Life Extension Foundation that issued the original warnings about who should not take melatonin. These warnings were based on preliminary findings, and in two instances the Foundation was overly cautious.

First, we suggested that prostate cancer patients might want to avoid high doses of melatonin. However, subsequent studies indicated that prostate cancer patients could benefit from moderate doses of melatonin, though the Foundation still advises prostate cancer patient to have their blood tested for prolactin. Melatonin could possibly elevate prolactin secretion, and if this were to happen in a prostate-cancer patient, the drug Dostinex could be used to suppress prolactin so that the melatonin could continue to be taken (in moderate doses of 1 to 6 mg each night).

The Foundation also stated that ovarian cancer patients should avoid melatonin until more is known about the effects of high doses of melatonin on this form of cancer.

However, a study published in Oncology Reports (Greece), 1996, 3/5 (947-949), indicates that high doses of melatonin may be beneficial in treating ovarian cancer. In this study, 40 mg of melatonin was given nightly, along with low doses of interleukin-2, to 12 advanced ovarian-cancer patients who had failed chemotherapy. While no complete response was seen, a partial response was achieved in 16 percent of patients, and a stable disease was obtained in 41 percent of the cases. This preliminary study suggests that melatonin is not contraindicated in advanced ovarian cancer patients.

Life Extension Foundation.

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