Summary
Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.
References
Lippman ME, Dickson RB, Bates S, Knabble C, Huff K, Swain S, McManaway M, Bronzert D, Kasid D, Gelmann EP: Autocrine and paracrine growth regulation of human breast cancer. Breast Cancer Res Treat 7: 59–70, 1986
Klijn JGM: Second International Symposium on ‘Hormonal manipulation of cancer: peptides, growth factors and new (anti) steroidal agents’. Ann Oncol 2: 183–189, 1991
Rosen N, Yee D, Lippman ME, Paik S, Cullen KJ: Insulin-like growth factors in human breast cancer. Breast Cancer Res Treat 18: S55-S62, 1991
Foekens JA, Portengen M, Janssen M, Klijn JGM: Insulin-like growth factor I receptors and insulin-like growth factor I activity in primary human breast cancer. Cancer 63: 2139–2147, 1989
Peyrat JP, Bonneterre J, Hecquet B, Vennin P, Louchez MM, Fournier C, Lefebvre J, Demaille A: Plasma insulin-like growth factor-1 concentrations in human breast cancer. Eur J Cancer 29A (4): 492–497, 1993
Rotwein P: Structure, evolution, expression and regulation of insulin-like growth factors I and II. Growth Factors 5: 3–18, 1991
Yee D, Favoni RE, Lippmann ME, Powell DR: Identification of insulin-like growth factor binding proteins in breast cancer cells. Breast Cancer Res Treat 18: 3–10, 1991
Reichlin S: Somatostatin (first of two parts). N Engl J Med 309: 1495–1501, 1983
Reichlin S: Somatostatin (second of two parts). N Engl J Med 309: 1556–1563, 1983
Parmar H, Bogden A, Mollard M, de Rouge B, Phillips RH, Lightman SL: Somatostatin and somatostatin analogues in oncology. Cancer Treat Rev 16: 95–115, 1989
Lamberts SW, Uitterlinden P, Verschoor L, van Dongen KL, del Pozo E: Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995. N Engl J Med 313: 1576–1580, 1985
Heron I, Kuhn JM, Mollard M, de Mouge M, Thomas F, Dero M, Vullenet P, Cancel A, Emy P, Houdent C, Wolf LM: Treatment of acromegalic patients with a long-acting formulation of the somatostatin analog BIM23014 (Abstract). J Endocrinol Invest 14: 43, 1991
Lamberts SWJ, Uitterlinden P, del Pozo E: SMS 201–995 induces a continuous decline in circulating growth hormone and somatostatin-C levels during therapy of acromegalic patients for over two years. J Clin Endocrinol Metab 65: 703–710, 1987
Setyono-Han B, Henkelman MS, Foekens JA, Klijn JGM: Direct inhibitory effect of somatostatin analogues on the growth of human breast cancer cells. Cancer Res 47: 1566–1570, 1987
Bootsma AH, van Eijck C, Schouten KK, Reubi JC, Wase B, Foekens JA, van Pel R, Zwarthoff EC, Lamberts SWJ, de Klein A: Somatostatin receptor-positive primary breast tumors: genetic, patient and tumor characteristics. Int J Cancer 54: 357–362, 1993
Prevost G, Lanson M, Thomas F, Verber N, Gonzalez W, Beavpain R, Starzec A, Bogden A: Molecular heterogeneity of somatostatin analogue BIM23014C receptors in human breast carcinoma cells using the chemical cross-linking assay. Cancer Res 52: 843–850, 1992
Reubi JC, Torhorst J: The relationship between somatostatin, epidermal growth factor and steroid hormone receptors in breast cancer. Cancer 64: 1254–1260, 1989
Manni A, Boucher AE, Demers LM, Harvey HA, Lipton A, Symmonds MA, Bartholomen M: Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. Breast Cancer Res Treat 14: 289–298, 1989
Vennin PH, Peyrat JP, Bonneterre J, Louchez MM, Harris AG, Demaille A: Effect of the long-acting somatostatin analogue SMS 201–995 (sandostatin) in advanced breast cancer. Anticancer Res 9: 153–156, 1989
Stolfi R, Parisi AM, Natali C, Iacobelli S: Advanced breast cancer: response to somatostatin. Anticancer Res 10: 203–204, 1990
Morere JF, Cour V, Breav JL, Boaziz C, Basin C, Israel L: Stabilizing effect of BIM23014, a long-acting somatostatin analog, in 30 cases of advanced breast cancer. A Phase II study. (Abstract). Proc. American Society of Clinical Oncology 8: 47, 1989
Canobbio L, Cannata D, Miglietta L, Boccardo F: Somatuline and tamoxifen in postmenopausal breast cancer patients. Ann NY Acad Sci 698: 362–366, 1993
Kuhn JM: Lanreotide: information for clinical investigators. pp. 46-47, 1992
World Health Organization: Handbook for reporting results of cancer treatment. WHO offset publication No. 48, Geneva, 1979
Gehan EA: The determination of the number of patients in a preliminary and follow-up trial of a new chemotherapeutic agent. J Chron Dis 13: 345–352, 1961
Pollak M, Costantino J, Polychronakos C, Blauer SA, Guyda H, Redmond C, Fisher B, Margolese R: Effect of tamoxifen on serum insulin-like growth factor-1 levels in stage I breast cancer patients. J Natl Cancer Inst 82(21): 1693–1697, 1990
Parmar H, Phillips RH, Lightman SL: Somatostatin analogues: mechanisms of action. In: Hoffken K (ed) Peptides in Oncology II. Springer-Verlag, Berlin, 1992, p. 7
Klijn JGM, Hoff AM, Planting AST, Verwe JJ, Kok J, Lamberts SWJ, Portengen H, Foekens JA: Treatment of patients with metastatic pancreatic and gastrointestinal tumors with the somatostatin analogue sandostatin: a Phase II study including endocrine effects. Br J Cancer 62: 627–630, 1990
Bonneterre J, Pion JM, Adenis A, Peyrat JP, Henana S, Thomas F: Bromocriptin and lanreotide in advanced breast cancer: a phase II study (Abstract). Eur J Cancer 29A(6): S84, 1993
Parmar H, Charlton CDA, Phillips RH, Edwards L, Bejot JL, Thomas F, Lightman SL: Therapeutic response to somatostatin analogue BIM23014 in metastatic prostatic cancer. Clin Exp Metastasis 10: 3–11, 1992
Kvols KL, Reubi JC: Role of somatostatin analogues in therapy of gastrointestinal neoplasia. (Abstract). Proc of the World Congress of Gastroenterology, Sidney, 1990. Abs. no. S43
Yamada Y, Post SR, Wang K, Tager HS, Bell GI, Seino S: Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract and kidney. Proc Natl Acad Sci U.S.A. 89: 251–255, 1992
Rohrer L, Raulf F, Bruns C, Buetlner R, Hofstaedter F, Schule R: Cloning and characterization of a fourth human somatostatin receptor. Proc Natl Acad Sci U.S.A. 90: 4196–4200, 1993
Lamberts SWJ, Bakker WH, Reubi JC, Krenning EP: Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 323: 1246–1249, 1990
Klijn JGM: Somatostatin analogues and receptors in the treatment of breast and other cancers (Abstract). Eur J Cancer 29A (supp 6): 91
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Di Leo, A., Ferrari, L., Bajetta, E. et al. Biological and clinical evaluation of Lanreotide (BIM 23014), a somatostatin analogue, in the treatment of advanced breast cancer. Breast Cancer Res Tr 34, 237–244 (1995). https://doi.org/10.1007/BF00689715
Issue Date:
DOI: https://doi.org/10.1007/BF00689715