Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172780X
Vol.24 Nos.3/4, Jun-Aug 2003
Total pineal endocrine substitution therapy of metastatic cancer
pineal endocrine substitution therapy (TPEST) as a new neuroendocrine
palliative treatment of untreatable metastatic solid tumor
patients: A phase II study
Lissoni 1, Fabio Malugani 1, Fernando Brivio
Alessandra Piazza 1, Carmen Vintimilla 1, Luisa
& Gabriele Tancini 1
Division of Radiation Oncology, S. Gerardo Hospital, Monza
2. Third Surgical Division, S. Gerardo Hospital, Monza (Milan),
October 27, 2002
Accepted: November 19, 2002
melatonin, pineal gland, pineal indoles, supportive care
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.
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.
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: 410).
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.
Copyright © Neuroendocrinology Letters 2003
Society of Integrated Sciences
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