Skip to main content
PMC home page
Gut logoLink to Gut
. 1996 Mar;38(3):430–438. doi: 10.1136/gut.38.3.430

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

R Arnold 1, M E Trautmann 1, W Creutzfeldt 1, R Benning 1, M Benning 1, C Neuhaus 1, R Jürgensen 1, K Stein 1, H Schäfer 1, C Bruns 1, H J Dennler 1
PMCID: PMC1383075  PMID: 8675099

Abstract

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.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison D. J., Jordan H., Hennessy O. Therapeutic embolisation of the hepatic artery: a review of 75 procedures. Lancet. 1985 Mar 16;1(8429):595–599. doi: 10.1016/s0140-6736(85)92142-7. [DOI] [PubMed] [Google Scholar]
  2. Boden G., Ryan I. G., Eisenschmid B. L., Shelmet J. J., Owen O. E. Treatment of inoperable glucagonoma with the long-acting somatostatin analogue SMS 201-995. N Engl J Med. 1986 Jun 26;314(26):1686–1689. doi: 10.1056/NEJM198606263142606. [DOI] [PubMed] [Google Scholar]
  3. Buchanan K. D. Effects of sandostatin on neuroendocrine tumours of the gastrointestinal system. Recent Results Cancer Res. 1993;129:45–55. doi: 10.1007/978-3-642-84956-5_3. [DOI] [PubMed] [Google Scholar]
  4. Capella C., Heitz P. U., Höfler H., Solcia E., Klöppel G. Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Digestion. 1994;55 (Suppl 3):11–23. doi: 10.1159/000201197. [DOI] [PubMed] [Google Scholar]
  5. Carrasco C. H., Charnsangavej C., Ajani J., Samaan N. A., Richli W., Wallace S. The carcinoid syndrome: palliation by hepatic artery embolization. AJR Am J Roentgenol. 1986 Jul;147(1):149–154. doi: 10.2214/ajr.147.1.149. [DOI] [PubMed] [Google Scholar]
  6. Clements D., Elias E. Regression of metastatic vipoma with somatostatin analogue SMS 201-995. Lancet. 1985 Apr 13;1(8433):874–875. doi: 10.1016/s0140-6736(85)92235-4. [DOI] [PubMed] [Google Scholar]
  7. Creutzfeldt W., Bartsch H. H., Jacubaschke U., Stöckmann F. Treatment of gastrointestinal endocrine tumours with interferon-alpha and octreotide. Acta Oncol. 1991;30(4):529–535. doi: 10.3109/02841869109092413. [DOI] [PubMed] [Google Scholar]
  8. Deguchi H., Deguchi K., Tsukada T., Murashima S., Iwasaki E., Tsuda M., Kobayashi T., Shirakawa S. Long-term survival in a patient with malignant carcinoid treated with high-dose octreotide. Intern Med. 1994 Feb;33(2):100–102. doi: 10.2169/internalmedicine.33.100. [DOI] [PubMed] [Google Scholar]
  9. Evers B. M., Parekh D., Townsend C. M., Jr, Thompson J. C. Somatostatin and analogues in the treatment of cancer. A review. Ann Surg. 1991 Mar;213(3):190–198. doi: 10.1097/00000658-199103000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hanssen L. E., Schrumpf E., Kolbenstvedt A. N., Tausjø J., Dolva L. O. Recombinant alpha-2 interferon with or without hepatic artery embolization in the treatment of midgut carcinoid tumours. A preliminary report. Acta Oncol. 1989;28(3):439–443. doi: 10.3109/02841868909111219. [DOI] [PubMed] [Google Scholar]
  11. Joensuu H., Kätkä K., Kujari H. Dramatic response of a metastatic carcinoid tumour to a combination of interferon and octreotide. Acta Endocrinol (Copenh) 1992 Feb;126(2):184–185. doi: 10.1530/acta.0.1260184. [DOI] [PubMed] [Google Scholar]
  12. Johnson L. A., Lavin P., Moertel C. G., Weiland L., Dayal Y., Doos W. G., Geller S. A., Cooper H. S., Nime F., Massé S. Carcinoids: the association of histologic growth pattern and survival. Cancer. 1983 Mar 1;51(5):882–889. doi: 10.1002/1097-0142(19830301)51:5<882::aid-cncr2820510522>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  13. Joseph K., Stapp J., Reinecke J., Höffken H., Benning R., Neuhaus C., Trautmann M. E., Schwerk W. B., Arnold R. Rezeptorszintigraphie bei endokrinen gastroenteropankreatischen Tumoren. Dtsch Med Wochenschr. 1992 Jun 26;117(26):1025–1028. doi: 10.1055/s-2008-1062406. [DOI] [PubMed] [Google Scholar]
  14. Kraenzlin M. E., Ch'ng J. L., Wood S. M., Carr D. H., Bloom S. R. Long-term treatment of a VIPoma with somatostatin analogue resulting in remission of symptoms and possible shrinkage of metastases. Gastroenterology. 1985 Jan;88(1 Pt 1):185–187. doi: 10.1016/s0016-5085(85)80153-0. [DOI] [PubMed] [Google Scholar]
  15. Kvols L. K., Buck M. Chemotherapy of endocrine malignancies: a review. Semin Oncol. 1987 Sep;14(3):343–353. [PubMed] [Google Scholar]
  16. Kvols L. K., Buck M., Moertel C. G., Schutt A. J., Rubin J., O'Connell M. J., Hahn R. G. Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). Ann Intern Med. 1987 Aug;107(2):162–168. doi: 10.7326/0003-4819-107-2-162. [DOI] [PubMed] [Google Scholar]
  17. Kvols L. K., Moertel C. G., O'Connell M. J., Schutt A. J., Rubin J., Hahn R. G. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986 Sep 11;315(11):663–666. doi: 10.1056/NEJM198609113151102. [DOI] [PubMed] [Google Scholar]
  18. Kvols L. K., Reubi J. C., Horisberger U., Moertel C. G., Rubin J., Charboneau J. W. The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide. Yale J Biol Med. 1992 Sep-Oct;65(5):505–536. [PMC free article] [PubMed] [Google Scholar]
  19. Lewin M. J. The somatostatin receptor in the GI tract. Annu Rev Physiol. 1992;54:455–468. doi: 10.1146/annurev.ph.54.030192.002323. [DOI] [PubMed] [Google Scholar]
  20. Makowka L., Tzakis A. G., Mazzaferro V., Teperman L., Demetris A. J., Iwatsuki S., Starzl T. E. Transplantation of the liver for metastatic endocrine tumors of the intestine and pancreas. Surg Gynecol Obstet. 1989 Feb;168(2):107–111. [PMC free article] [PubMed] [Google Scholar]
  21. Maton P. N., O'Dorisio T. M., Howe B. A., McArthur K. E., Howard J. M., Cherner J. A., Malarkey T. B., Collen M. J., Gardner J. D., Jensen R. T. Effect of a long-acting somatostatin analogue (SMS 201-995) in a patient with pancreatic cholera. N Engl J Med. 1985 Jan 3;312(1):17–21. doi: 10.1056/NEJM198501033120104. [DOI] [PubMed] [Google Scholar]
  22. Moertel C. G., Hanley J. A., Johnson L. A. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980 Nov 20;303(21):1189–1194. doi: 10.1056/NEJM198011203032101. [DOI] [PubMed] [Google Scholar]
  23. Moertel C. G., Kvols L. K., O'Connell M. J., Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. 1991 Jul 15;68(2):227–232. doi: 10.1002/1097-0142(19910715)68:2<227::aid-cncr2820680202>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  24. Moertel C. G., Lefkopoulo M., Lipsitz S., Hahn R. G., Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519–523. doi: 10.1056/NEJM199202203260804. [DOI] [PubMed] [Google Scholar]
  25. Nold R., Frank M., Kajdan U., Trost U., Klose K. J., Arnold R. Kombinierte Behandlung metastasierter endokriner Tumoren des Gastrointestinaltrakts mit Octreotid und Interferon-Alpha. Z Gastroenterol. 1994 Apr;32(4):193–197. [PubMed] [Google Scholar]
  26. Oberg K., Funa K., Alm G. Effects of leukocyte interferon on clinical symptoms and hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome. N Engl J Med. 1983 Jul 21;309(3):129–133. doi: 10.1056/NEJM198307213090301. [DOI] [PubMed] [Google Scholar]
  27. Oberg K., Norheim I., Lind E., Alm G., Lundqvist G., Wide L., Jonsdottir B., Magnusson A., Wilander E. Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results. Cancer Treat Rep. 1986 Nov;70(11):1297–1304. [PubMed] [Google Scholar]
  28. Rothmund M., Stinner B., Arnold R. Endocrine pancreatic carcinoma. Eur J Surg Oncol. 1991 Apr;17(2):191–199. [PubMed] [Google Scholar]
  29. Ruskoné A., René E., Chayvialle J. A., Bonin N., Pignal F., Kremer M., Bonfils S., Rambaud J. C. Effect of somatostatin on diarrhea and on small intestinal water and electrolyte transport in a patient with pancreatic cholera. Dig Dis Sci. 1982 May;27(5):459–466. doi: 10.1007/BF01295657. [DOI] [PubMed] [Google Scholar]
  30. Saltz L., Trochanowski B., Buckley M., Heffernan B., Niedzwiecki D., Tao Y., Kelsen D. Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors. Cancer. 1993 Jul 1;72(1):244–248. doi: 10.1002/1097-0142(19930701)72:1<244::aid-cncr2820720143>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  31. Santangelo W. C., O'Dorisio T. M., Kim J. G., Severino G., Krejs G. J. Pancreatic cholera syndrome: effect of a synthetic somatostatin analog on intestinal water and ion transport. Ann Intern Med. 1985 Sep;103(3):363–367. doi: 10.7326/0003-4819-103-3-363. [DOI] [PubMed] [Google Scholar]
  32. Shepherd J. J., Senator G. B. Regression of liver metastases in patient with gastrin-secreting tumour treated with SMS 201-995. Lancet. 1986 Sep 6;2(8506):574–574. doi: 10.1016/s0140-6736(86)90139-x. [DOI] [PubMed] [Google Scholar]
  33. Smith D. B., Scarffe J. H., Wagstaff J., Johnston R. J. Phase II trial of rDNA alfa 2b interferon in patients with malignant carcinoid tumor. Cancer Treat Rep. 1987 Dec;71(12):1265–1266. [PubMed] [Google Scholar]
  34. Sridhar K. S., Holland J. F., Brown J. C., Cohen J. M., Ohnuma T. Doxorubicin plus cisplatin in the treatment of apudomas. Cancer. 1985 Jun 1;55(11):2634–2637. doi: 10.1002/1097-0142(19850601)55:11<2634::aid-cncr2820551117>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  35. Vinik A., Moattari A. R. Use of somatostatin analog in management of carcinoid syndrome. Dig Dis Sci. 1989 Mar;34(3 Suppl):14S–27S. doi: 10.1007/BF01536042. [DOI] [PubMed] [Google Scholar]
  36. Wiedenmann B., Räth U., Rädsch R., Becker F., Kommerell B. Tumor regression of an ileal carcinoid under the treatment with the somatostatin analogue SMS 201-995. Klin Wochenschr. 1988 Jan 15;66(2):75–77. doi: 10.1007/BF01713015. [DOI] [PubMed] [Google Scholar]
  37. von Schrenck T., Howard J. M., Doppman J. L., Norton J. A., Maton P. N., Smith F. P., Vinayek R., Frucht H., Wank S. A., Gardner J. D. Prospective study of chemotherapy in patients with metastatic gastrinoma. Gastroenterology. 1988 Jun;94(6):1326–1334. doi: 10.1016/0016-5085(88)90670-1. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES