Download Is there a role for melatonin in supportive care? Lissoni P. Support

Psycho-Neuro-Immunotherapy
Complex Bionetwork exists between mind (psycho), nervous system and immune system as
multidirectional feedback communications. When this complex system in the body gets
weakened due to chronic negative stress, it is the immune system that constantly keeps
surveillance in the body that might receives the brunt of the stress. Therefore, clinical trials in
this area have evoked lot of interest in the control of cancer and other diseases.
One such agent that has been found to modulate the Psycho-Neuro-Immuno system is
melatonin. Melatonin, a neurohormone produced mainly by the pineal gland located in the
base of the brain. Melatonin appears to regulate cell dynamics, including the proliferative and
maturational stages of virtually all haemopoietic and immune cells lineages involved in body
defense - not only Natural Killer cells but also T and B lymphocytes, granulocytes and
monocytes - in both bone marrow and tissues (all these cells are the one that attack the
infective agents and cancer cells).
Melatonin is available as a tablet and is presently used to overcome the jetlag. While the
optimal dose of melatonin for treating different types of cancer has not yet been established,
the many clinical studies by Lissoni and colleagues have shown that doses of 10-20 mg of
melatonin, nightly, are beneficial to cancer patients. Those recently diagnosed with slowgrowing or early-stage cancer may wish to consider supplementing with 3 to 6 mg melatonin
nightly; the latter dose may be reserved for early-stage cancer patients who suffer from
disturbed sleep patterns. Most clinical studies have shown that patients with late-stage,
advanced, or untreatable cancer, or those with cancer metastasis, benefit from
supplementation with 20 mg of melatonin.
Caution: Not all the published literature favours its use in the control of cancer and along with
cancer therapies. Please refer to the articles that have not favoured its use in cancer, at the
end of this section.
Results in favour of use of Melatonin :
 Is there a role for melatonin in supportive care? Lissoni P. Support Care Cancer. 2002
Mar;10(2):110-6. Epub 2001 Nov 13

A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal
hormone melatonin in untreatable advanced hematologic malignancies. Lissoni P
Anticancer Res. 2000 May-Jun;20(3B):2103-5.

Breast cancer and effect of melatonin: Melatonin and Breast Cancer Risk: women who
work the night shift may face an increased risk of breast cancer

Braintumors and effect of melatonin: The pineal hormone melatonin may be able to
improve the survival time and the quality of life in patients with brain metastases due to
solid tumors

Braintumors and effect of melatonin: Increased survival time in brain glioblastomas by a
radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy
alone

Colorectal cancer and effect of melatonin: Night-shift work and risk of colorectal cancer in
the nurses’ health study

Colorectal cancer and effect of melatonin: the efficacy of weekly low-dose CPT-11 in
pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily
administration of the pineal hormone MLT, according to the results previously reported for
other chemotherapeutic agents.

Hematologic malignancies and effect of melatonin: the concomitant administration of lowdose IL-2 plus the pineal hormone MLT may prolong the survival time in untreatable
advanced hematologic malignancies, with results comparable to those previously reported
using a more toxic immunotherapy, consisting of high-dose IL-2 alone.

Lung cancer (non-small-cell) and effect of melatonin: Randomised study confirms, in a
considerable number of patients and for a long follow-up period, the possibility to improve
the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant
administration of melatonin

Solid tumors and effect of melatonin: cancer neuroimmunotherapy with low-dose IL-2 and
the pineal hormone melatonin may prolong survival time and improve the quality of life of
patients with metastatic solid tumours who do not respond to conventional therapies

Solid tumors and effect of melatonin: Decreased toxicity and increased efficacy of cancer
chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with
poor clinical status

TACE = transcatheter arterial chemo embolization and effect of melatonin: With definite
protection and treatment effect on the liver function damage caused by TACE, MLT =
Melatonin can enhance the immunological activities of patients. It also can improve the
effect of TACE by increasing the survival and resection rate after two-stage operation

The role of melatonin in immuno-enhancement: potential application in cancer. Miller
SC et al, Int J Exp Pathol. 2006 Apr;87(2):81-7.

Melatonin in pathogenesis and therapy of cancer. Ravindra T et al. Indian Journal of
Medical Sciences, 2006. http://www.indianjmedsci.org/text.asp?2006/60/12/523/28983

Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous lowdose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced
antitumor immunity by blocking the opioid system. Neuro Endocrinol Lett. 2002
Aug;23(4):341-4. Lissoni P, Malugani F, Malysheva O, Kozlov V, Laudon M, Conti A,
Maestroni G.

Stress, cancer and circadian rhythm of melatonin]. Kwiatkowski F, Abrial C, Gachon F,
Chevrier R, Cure H, Chollet P. Pathol Biol (Paris). 2005 Jun;53(5):269-72. Epub 2005
Jan 20. Review. French.
Results not in favour of use of Melatonin :
Melatonin protected both normal and cancer cells against genotoxic treatment and apoptosis
induced by a chemotherapeutic drug idarubicin. One can conclude that despite its recognized
potential as an antioxidant, melatonin should be considered with caution when used in
combination with cancer chemotherapy agents, especially in the case of leukemias.
(Majsterek I et al. A comparison of the action of amifostine and melatonin on DNA-damaging
effects and apoptosis induced by idarubicin in normal and cancer cells.J Pineal Res. 2005
May;38(4):254-63)