Journal Mobile Options
Table of Contents
Vol. 88, No. 1, 2008
Issue release date: July 2008
Neuroendocrinology 2008;88:53–58

Treatment with Combined Streptozotocin and Liposomal Doxorubicin in Metastatic Endocrine Pancreatic Tumors

Fjällskog M.-L.H. · Janson E.T. · Falkmer U.G. · Vatn M.H. · Öberg K.E. · Eriksson B.K.
Departments of aOncology, Radiology and Clinical Immunology, and bMedical Sciences, Uppsala University, Uppsala, Sweden; cDepartment of Oncology, University Hospital, Trondheim, and dDepartment of Medicine, Rikshospitalet and Faculty of Medicine, University of Oslo, EpiGen Institute, Ahus, Oslo, Norway

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. Background: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. Methods: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m2 of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. Results: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. Conclusion: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Öberg K: Neuroendocrine gastrointestinal tumors – a condensed overview of diagnosis and treatment. Ann Oncol 1999;10:S3–S8.
  2. Plöckinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, Goede A, Caplin M, Oberg K, Reubi JC, Nilsson O, Delle Fave G, Ruszniewski P, Ahlman H, Wiedenmann B; European Neuroendocrine Tumour Society: Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 2004;80:394–424.
  3. de Herder WW, O’Toole D, Rindi G, Wiedenmann B (eds): ENETS consensus guidelines for the management of patients with digestive neuroendocrine tumors. 1. Stomach, duodenum and pancreas. Neuroendocrinology 2006;84:151–216.

    External Resources

  4. Welbourn RB, Wood SM, Polak JM, Bloom SR: Pancreatic endocrine tumors; in Bloom SR, Polak JR (eds): Gut Hormones. London, Churchill Livingstone, 1981, pp 547–554.
  5. Moertel CG, Hanley JA, Johnson LA: Streptozotocin alone compared with streptozotocin in the treatment of advanced islet cell carcinoma. N Engl J Med 1980;303:1189–1194.
  6. Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D: Streptozotocin-doxorubicin, streptozotocin-fluorouracil, or chlorozotocin in the treatment of advanced islet cell carcinoma. N Engl J Med 1992;326:519–523.
  7. Jensen BV, Skovsgaard T, Nielsen SL: Functional monitoring of anthracyclin cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol 2002;13:699–709.
  8. Eriksson B, Öberg K: An update of the medical treatment of malignant endocrine pancreatic tumors. Acta Oncol 1993;32:203–208.
  9. Jensen BV: Cardiotoxic consequences of anthracyclin-containing therapy in patients with breast cancer. Semin Oncol 2006;33(3 suppl 8):S15–S21.

    External Resources

  10. Berry G, Billingham M, Alderman E, Richardson P, Torti F, Lum B, Patek A, Martin FJ: The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi’s sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol 1998;9:711–716.
  11. O’Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group: Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCI (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 2004;15:440–449.
  12. Uyar D, Kulp B, Peterson G, Zanotti K, Markman M, Belinson J: Cardiac safety profile of prolonged (> or = 6 cycles) pegylated liposomal doxorubicin in patients with gynecologic malignancies. Gynecol Oncol 2004;94:147–151.
  13. Yildirim Y, Gultekin E, Avci ME, Inal MM, Yunus S, Tinar S: Cardiac safety profile of pegylated liposomal doxorubicin reaching or exceeding lifetime cumulative doses of 550 mg/m2 in patients with recurrent ovarian and peritoneal cancer. Int J Gynecol Cancer 2007; Epub ahead of print.
  14. Oberg K, Astrup L, Eriksson B, Falkmer SE, Falkmer UG, Gustafsen J, Haglund C, Knigge U, Vatn MH, Välimäki M; Nordic NE Tumour Group: Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Acta Oncol 2004;43:617–636.
  15. Cheng PNM, Saltz LB: Failure to confirm major objective antitumor activity for streptozotocin and doxorubicin in the treatment of patients with advanced islet cell carcinoma. Cancer 1999;86:944–948.
  16. Delaunoit T, Ducreux M, Boige V, Dromain C, Sabourin JC, Duvillard P, Schlumberger M, de Baere T, Rougier P, Ruffie P, Elias D, Lasser P, Baudin E: The doxorubicin-streptozotocin combination for the treatment of advanced well-differentiated pancreatic endocrine carcinoma: a judicious option? Eur J Cancer 2004;40:515–520.
  17. Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, Yao JC: Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 2004;22:4762–4771.
  18. Toumpanakis C, Meyer T, Caplin ME: Cytotoxic treatment including embolization/chemoembolization for neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2007;21:131–144.
  19. Eriksson B, Skogseid B, Lundqvist G, Wide L, Wilander E, Oberg K: Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors. Cancer 1990;65:1883–1990.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50