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

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 require 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.

Efficacy of bromocriptine in the treatment of metastatic breast cancer- and prostate cancer-related hyperprolactinemia.

OBJECTIVE: Hyperprolactinemia is a frequent evidence occurring in both metastatic breast cancer and prostate cancer, and it has been proven to be associated with poor prognosis and reduced efficacy of the anticancer therapies. Therefore, the pharmacological control of cancer-related hyperprolactinemia could improve the prognosis of advanced breast and prostate carcinomas. Unfortunately, at present it is still controversial which may be the treatment of cancer-related hyperprolactinemia, which could depend at least in part on a direct autocrine production by cancer cells themselves. The present study was performed to evaluate the acute effects of the long-acting dopaminergic agonist bromocriptine on cancer-related hyperprolactinemia. METHODS: The study included 10 women affected by metastatic breast cancer and 10 men with metastatic prostate cancer, showing persistent hyperprolactinemia. Venous blood samples were collected before bromocriptine, and 2, 4, 10 and 24 hours after bromocriptine administration (2.5 mg orally) serum levels of PRL were measured with the double antibody RIA method. RESULTS: Bromocriptine induced a normalization of PRL levels in both groups of patients with breast and prostate cancers. Moreover, mean levels of PRL persisted significantly lower than those found before therapy during the whole 24-hour circadian period. DISCUSSION: This preliminary study shows that low-dose bromocriptine is sufficient to acutely normalize PRL secretion in both metastatic breast cancer and prostate carcinoma patients, irrespectively of the mechanisms involved in inducing cancer-related hyperprolactinemia. Therefore, low-dose bromocriptine could be recommended in association with the classical antitumor therapies in the treatment of metastatic breast cancer and prostate carcinoma patients showing cancer-related hyperprolactinemia, in an attempt to improve the efficacy of anticancer therapies themselves.