Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up

Abstract

Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer.

Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive.

In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone.

Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy.

An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy.

Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms.

With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy.

Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1.

Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects.

Large phase III trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

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

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- 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.