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NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172–780X

NEL Vol.24 Nos.3/4, Jun-Aug 2003

ORIGINAL ARTICLE

Running Title:
Total pineal endocrine substitution therapy of metastatic cancer

2003; 24:259262
pii: NEL243403A18
PMID: 14523367

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Total pineal endocrine substitution therapy (TPEST) as a new neuroendocrine palliative treatment of untreatable metastatic solid tumor patients: A phase II study

Paolo Lissoni 1, Fabio Malugani 1, Fernando Brivio 2,
Alessandra Piazza 1, Carmen Vintimilla 1, Luisa Giani 1
& Gabriele Tancini 1

1. Division of Radiation Oncology, S. Gerardo Hospital, Monza (Milan), Italy.
2. Third Surgical Division, S. Gerardo Hospital, Monza (Milan), Italy.

Submitted: October 27, 2002
Accepted: November 19, 2002

Key words:
melatonin, pineal gland, pineal indoles, supportive care

 

Abstract

OBJECTIVES: It is known since many years that the pineal gland plays an anticancer role, and melatonin (MLT), the most investigated pineal hormone, has been proven to exert antitumor activity. However, MLT would not be the only hormone responsible for the antitumor action of the pineal gland. In fact, recent advances in the pineal investigations have shown that pineal indoles other than MLT may also exert anticancer activity, namely the three main indoles, consisting of 5-methoxytriptamine (5-MTT), 5-methoxytryptophol (5-MTP) and 5-methoxy-indole acetic acid (5-MIA). Cancer progression has appeared to be associated with a concomitant decline in the pineal endocrine function. Therefore , the replacement of a complete pineal function in the advanced cancer patients would required the exogenous administration of the overall four pineal indoles. Several clinical studies have shown that MLT alone at pharmacological doses may induce a control of the neoplastic progression in about 30% of untreatable metastatic solid tumor patients. The present study was performed in an attempt to evaluate the therapeutic of a total pineal endocrine substitution therapy with its four indole hormones in cancer patients, for whom no other conventional therapy was available.

METHODS: The study included 14 metastatic solid tumor patients, who had failed to respond to the conventional anticancer therapies. The pineal indoles were given orally according to a schedule elaborated in an attempt to reproduce their physiological circadian secretion during the daily photoperiod. MLT was given at 20 mg/day during the night, whereas the other indoles were given at 1 mg/day, by administering 5-MIA in the morning, 5-MTP at noon and 5-MTT in the afternoon.

RESULTS: A disease-control was achieved in 9/14 (64%) patients, consisting of partial response (PR) in one patient and stable disease (SD) in the other 8 patients. The median time of disease-control (PR + SD) was 6 months (range: 4–10).

CONCLUSIONS: This preliminary study shows that a total pineal endocrine replacement therapy by an exogenous administration of the overall four pineal indoles may induce a disease-control in about 60% of untreatable metastatic solid tumor patients. Then, these results would be clearly superior with respect to those described with MLT alone, by confirming in humans that MLT is not the only hormone responsible for the anticancer property of the pineal gland. Since Cartesius was the first author who suggested the fundamental role of the pineal in the connection between consciousness and biological life, this therapy could be defined as a Cartesian therapy.

 

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