Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours.

R Arnold, M E Trautmann, W Creutzfeldt, R Benning, M Benning, C Neuhaus, R Jürgensen, K Stein, H Schäfer, C Bruns, H J Dennler

Department of Internal Medicine, Philipps-University, Baldingerstrasse, Germany.

Antiproliferative treatment of patients with metastatic endocrine gastroenteropancreatic tumours (GEP) is based mainly on chemotherapeutic protocols whereby drug toxicity is a major handicap. Octreotide is the first choice in the control of hormone mediated symptoms. From retrospective and a few prospective studies it has been suggested that octreotide exhibits antiproliferative properties. The prospective German Sandostatin multicentre phase II trial investigated the effects of 200 micrograms octreotide thrice daily for one year on tumour growth and endocrine abnormalities in 103 patients. Octreotide treatment was continued in those patients responding to the drug until tumour progression occurred. In 28 of those with tumour progression during 200 micrograms thrice daily octreotide dose was increased to 500 micrograms thrice daily. The study sample consisted of 52 patients with computed tomography confirmed tumour progression and 13 patients with stable disease before octreotide treatment, whereas no preobservation period was available in 38 patients. Nineteen patients (36.5%) with computed tomography confirmed tumour progression experienced stabilisation of tumour growth lasting for at least three months. Median duration of stable disease was 18 months. At month 12, stable disease continued in 12 patients, declined after 24 months to nine patients, and after 36 months to five patients. Tumour regression has not been seen in this or other subgroups. In the subgroup with stable disease before octreotide, stable disease continued in 53.8% of patients over 12 months. Increase of octreotide dose to 500 micrograms thrice daily did not influence progression seen during the lower dose with the exception of one patient in whom tumour progression changed to stable disease. No association of tumour size response and patients' characteristics could be detected. The results suggest that octreotide inhibits tumour growth in patients with metastasised endocrine GEP tumours. The antiproliferative effect is, at least in some patients, longlasting. Currently, octreotide can only be recommended as an antiproliferative drug if patients with clearly progressive disease show stabilisation after treatment for three to six months.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Rinke, A., Muller, H.-H., Schade-Brittinger, C., Klose, K.-J., Barth, P., Wied, M., Mayer, C., Aminossadati, B., Pape, U.-F., Blaker, M., Harder, J., Arnold, C., Gress, T., Arnold, R. (2009). Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group. JCO 27: 4656-4663 [Abstract] [Full Text]  
• CHADHA, M. K., LOMBARDO, J., MASHTARE, T., WILDING, G. E., LITWIN, A., RACZYK, C., GIBBS, J. F., KUVSHINOFF, B., JAVLE, M. M., IYER, R. V. (2009). High-dose Octreotide Acetate for Management of Gastroenteropancreatic Neuroendocrine Tumors. Anticancer Res 29: 4127-4130 [Abstract] [Full Text]  
• Durante, C., Boukheris, H., Dromain, C., Duvillard, P., Leboulleux, S., Elias, D., de Baere, T., Malka, D., Lumbroso, J., Guigay, J., Schlumberger, M., Ducreux, M., Baudin, E. (2009). Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma. Endocr Relat Cancer 16: 585-597 [Abstract] [Full Text]  
• AGARWAL, G., OBIDEEN, K., WEHBI, M. (2008). Carcinoid tumors: What should increase our suspicion?. Cleveland Clinic Journal of Medicine 75: 849-855 [Abstract] [Full Text]  
• Pinchot, S. N., Holen, K., Sippel, R. S., Chen, H. (2008). Carcinoid Tumors. The Oncologist 13: 1255-1269 [Abstract] [Full Text]  
• Ardill, J. E S (2008). Circulating markers for endocrine tumours of the gastroenteropancreatic tract. Ann Clin Biochem 45: 539-559 [Abstract] [Full Text]  
• Grozinsky-Glasberg, S., Shimon, I., Korbonits, M., Grossman, A. B (2008). Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms. Endocr Relat Cancer 15: 701-720 [Abstract] [Full Text]  
• Debono, M., Hon, L.-Q., Bax, N., Blakeborough, A., Newell-Price, J. (2008). Gluteal Nodules in Patients with Metastatic Midgut Carcinoid Disease Treated with Depot Somatostatin Analogs. J. Clin. Endocrinol. Metab. 93: 1860-1864 [Abstract] [Full Text]  
• Ho, A. S., Picus, J., Darcy, M. D., Tan, B., Gould, J. E., Pilgram, T. K., Brown, D. B. (2007). Long-Term Outcome After Chemoembolization and Embolization of Hepatic Metastatic Lesions from Neuroendocrine Tumors. Am. J. Roentgenol. 188: 1201-1207 [Abstract] [Full Text]  
• Kidd, M., Eick, G. N, Modlin, I. M, Pfragner, R., Champaneria, M. C, Murren, J. (2007). Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin. J Mol Endocrinol 38: 181-192 [Abstract] [Full Text]  
• Fazio, N, de Braud, F, Delle Fave, G, Oberg, K (2007). Interferon-{alpha} and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination?. Ann Oncol 18: 13-19 [Abstract] [Full Text]  
• Yao, J. C., Zhang, J. X., Rashid, A., Yeung, S.-C. J., Szklaruk, J., Hess, K., Xie, K., Ellis, L., Abbruzzese, J. L., Ajani, J. A. (2007). Clinical and In vitro Studies of Imatinib in Advanced Carcinoid Tumors. Clin. Cancer Res. 13: 234-240 [Abstract] [Full Text]  
• Butturini, G, Bettini, R, Missiaglia, E, Mantovani, W, Dalai, I, Capelli, P, Ferdeghini, M, Pederzoli, P, Scarpa, A, Falconi, M (2006). Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma. Endocr Relat Cancer 13: 1213-1221 [Abstract] [Full Text]  
• Galli, G, Zonefrati, R, Gozzini, A, Mavilia, C, Martineti, V, Tognarini, I, Nesi, G, Marcucci, T, Tonelli, F, Tommasi, M, Raggi, C C., Pinzani, P, Brandi, M L (2006). Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma.. Endocr Relat Cancer 13: 79-93 [Abstract] [Full Text]  
• Panzuto, F., Di Fonzo, M., Iannicelli, E., Sciuto, R., Maini, C. L., Capurso, G., Milione, M., Cattaruzza, M. S., Falconi, M., David, V., Ziparo, V., Pederzoli, P., Bordi, C., Fave, G. D. (2006). Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma. Ann Oncol 17: 461-466 [Abstract] [Full Text]  
• Ramage, J K, Davies, A H G, Ardill, J, Bax, N, Caplin, M, Grossman, A, Hawkins, R, McNicol, A M, Reed, N, Sutton, R, Thakker, R, Aylwin, S, Breen, D, Britton, K, Buchanan, K, Corrie, P, Gillams, A, Lewington, V, McCance, D, Meeran, K, Watkinson, A, on behalf of UKNETwork for neuroendocrine tumours, (2005). Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut 54: iv1-iv16 [Full Text]  
• Delaunoit, T., Rubin, J., Neczyporenko, F., Erlichman, C., Hobday, T. J. (2005). Somatostatin Analogues in the Treatment of Gastroenteropancreatic Neuroendocrine Tumors. Mayo Clin Proc. 80: 502-506 [Abstract]  
• Kouvaraki, M. A., Ajani, J. A., Hoff, P., Wolff, R., Evans, D. B., Lozano, R., Yao, J. C. (2004). Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas. JCO 22: 4762-4771 [Abstract] [Full Text]  
• Mundschenk, J., Unger, N., Schulz, S., Hollt, V., Schulz, S., Steinke, R., Lehnert, H. (2003). Somatostatin Receptor Subtypes in Human Pheochromocytoma: Subcellular Expression Pattern and Functional Relevance for Octreotide Scintigraphy. J. Clin. Endocrinol. Metab. 88: 5150-5157 [Abstract] [Full Text]  
• Faiss, S., Pape, U.-F., Bohmig, M., Dorffel, Y., Mansmann, U., Golder, W., Riecken, E. O., Wiedenmann, B. (2003). Prospective, Randomized, Multicenter Trial on the Antiproliferative Effect of Lanreotide, Interferon Alfa, and Their Combination for Therapy of Metastatic Neuroendocrine Gastroenteropancreatic Tumors--The International Lanreotide and Interferon Alfa Study Group. JCO 21: 2689-2696 [Abstract] [Full Text]  
• Strowski, M. Z., Kohler, M., Chen, H. Y., Trumbauer, M. E., Li, Z., Szalkowski, D., Gopal-Truter, S., Fisher, J. K., Schaeffer, J. M., Blake, A. D., Zhang, B. B., Wilkinson, H. A. (2003). Somatostatin Receptor Subtype 5 Regulates Insulin Secretion and Glucose Homeostasis. Mol. Endocrinol. 17: 93-106 [Abstract] [Full Text]  
• Kulaksiz, H, Eissele, R, Rossler, D, Schulz, S, Hollt, V, Cetin, Y, Arnold, R (2002). Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. Gut 50: 52-60 [Abstract] [Full Text]  
• Gibril, F., Venzon, D. J., Ojeaburu, J. V., Bashir, S., Jensen, R. T. (2001). Prospective Study of the Natural History of Gastrinoma in Patients with MEN1: Definition of an Aggressive and a Nonaggressive Form. J. Clin. Endocrinol. Metab. 86: 5282-5293 [Abstract] [Full Text]  
• Goebel, S. U., Heppner, C., Burns, A. L., Marx, S. J., Spiegel, A. M., Zhuang, Z., Lubensky, I. A., Gibril, F., Jensen, R. T., Serrano, J. (2000). Genotype/Phenotype Correlation of Multiple Endocrine Neoplasia Type 1 Gene Mutations in Sporadic Gastrinomas. J. Clin. Endocrinol. Metab. 85: 116-123 [Abstract] [Full Text]  
• Yu, F., Venzon, D. J., Serrano, J., Goebel, S. U., Doppman, J. L., Gibril, F., Jensen, R. T. (1999). Prospective Study of the Clinical Course, Prognostic Factors, Causes of Death, and Survival in Patients With Long-Standing Zollinger-Ellison Syndrome. JCO 17: 615-615 [Abstract] [Full Text]  
• Angeletti, S, Corleto, V D, Schillaci, O, Marignani, M, Annibale, B, Moretti, A, Silecchia, G, Scopinaro, F, Basso, N, Bordi, C, Delle Fave, G (1998). Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours. Gut 42: 792-794 [Abstract] [Full Text]  
• Wangberg, B., Nilsson, O., Johanson, V., Kolby, L., Forssell-Aronsson, E., Andersson, P., Fjalling, M., Tisell, L.-E., Ahlman, H. (1997). Somatostatin Receptors in the Diagnosis and Therapy of Neuroendocrine Tumors. The Oncologist 2: 50-58 [Abstract] [Full Text]