Five Year-Survival with High-Dose Melatonin and Other Antitumor Pineal Hormones in Advanced Cancer Patients Eligible for the Only Palliative Therapy

Published on Monday, 21 January 2019


Cancer progression has appeared at least in part to be due to a deficiency of the mechanisms responsible for the natural antitumor immune response. Moreover, more recent studies have demonstrated that cancer-related immunosuppression does not depend only of alterations of immune cells themselves, but also on an altered neuroendocrine regulation of the antitumor immune response, which is mainly inhibited by the mu-opioid agonists, such as beta-endorphin, and stimulated by the pineal gland through at least three immunostimulating molecules, able to exert a direct antiproliferative anticancer activity without any important biological toxicity, consisting of the indole hormones melatonin (MLT) and the 5-methoxytryptamine (5-MTT), and of the beta-carboline pinealine (PNL).

Finally, cancer progression has been shown to be constantly associated with a progressive decline in the endocrine function of the pineal gland, which could be involved in cancer dissemination itself. Then, the simple endocrine oncostatic pineal replacement therapy could counteract cancer growth and enhance the survival time, as suggested by preliminary clinical studies.

On the basis, a pineal endocrine regimen was proposed in a group of untreatable advanced solid tumor patients, for whom no other effective standard anticancer therapy was available.

The study included 212 patients, suffering from the most common tumor histotypes and eligible for the only best supportive care and with life expectancy less than 1 year.

All pineal indoles were given orally at the time corresponding to that of their maximal circadian secretion, every day without interruption until disease progression.

MLT was given at pharmacological doses (100 mg/day in the night period), while 5-MTT during the light period and PNL at the onset of the evening were administered at mild-pharmacological doses (5-MTT: 10 mg/day; PNL: 1 mg/day).

A disease control (DC) was achieved in 111/212 (52%) patients, with an objective tumor regression in 16/212 (8%), irrespectively of tumor histotype.

A 1-year and 5-year percentages of survival were achieved in 46% and 11%, respectively, and there were significantly higher in patients with DC than in the progressed ones.

Finally, the evidence of normal pretreatment values of lymphocyte-to-monocyte ratio (LMR) and/or their normalization on therapy have appeared to be associated with most favorable clinical results.

No biological toxicity occurred on pineal endocrine oncostatic treatment.

This study shows that an endocrine substitutive therapy with the most known antitumor pineal hormones may represent a new non-toxic inexpensive anticancer therapy, which can improve the survival and control cancer growth also in patients for whom no other effective therapy is available, at least to improve their life.

By concluding according to their results the palliative therapy of untreatable cancer patients for whom no other standard therapy available could be associated with a concomitant therapy with natural anticancer agents, namely the same pineal hormone.


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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up.