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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

Siegbert Faiss, Ulrich-Frank Pape, Michael Böhmig, Yvonne Dörffel, Ulrich Mansmann, Werner Golder, Ernst Otto Riecken, Bertram Wiedenmann

From the Departments of Gastroenterologie, Infektiologie, and Rheumatologie, Medizinische Klinik I Universitätsklinikum Benjamin Franklin, Freie Universität Berlin; Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Universitätsklinikum Charité (Campus Virchow Klinikum), and Medizinische Poliklinik, Universitätsklinikum Charité (Campus Mitte), Humboldt Universität zu Berlin; Abteilung für Radiologie und Nuklearmedizin, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin; and Institut für Medizinische Biometrie und Informatik, Universität Heidelberg, Heidelberg, Germany.

Address reprint requests to Bertram Wiedenmann, MD, Universitätsklinikum Charité, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Augustenburger Platz 1, D-13353 Berlin, Germany; email: bertram.wiedenmann{at}charite.de.

Purpose: Somatostatin analogs and interferon alfa control hormone-active/functional neuroendocrine gastroenteropancreatic tumors. In addition to hormonal control, variable degrees of antiproliferative effects for both agents have been reported. Until now, however, no prospective, randomized studies in therapy-naive patients have compared somatostatin analogs or interferon alfa alone with a combination of the two.

Methods: Eighty therapy-naive patients with histologically verified neuroendocrine tumor disease (primary localization: foregut, n = 36; midgut, n = 30; hindgut, n = 3; unknown, n = 11; functional, n = 29; nonfunctional, n = 51) were randomly treated either with lanreotide (1 mg three times a day administered subcutaneously [SC]) or interferon alfa (5 x 10⁶ U three times a week SC) or both. All patients had disease progression in the 3 months before study entry, verified with imaging procedures.

Results: Twenty-five patients were treated with lanreotide, 27 patients were treated with interferon alfa, and 28 patients were treated with the combination. Partial tumor remission was seen in four patients (one patient who received lanreotide, one patient who received interferon alfa, and two patients who received the combination). During the 12 months of therapy, stable disease was observed in 19 patients (seven patients who received lanreotide, seven patients who received interferon alfa, and five patients who received the combination), whereas tumor progression occurred in 14 of 25 patients (lanreotide), 15 of 27 patients (interferon alfa), and 14 of 28 patients (combination). Side effects leading to an interruption of therapy were more frequent in the combination group than in the monotherapy arms.

Conclusion: This prospective, randomized, multicenter study shows for the first time that somatostatin analogs, interferon alfa, or the combination of the two had comparable antiproliferative effects in the treatment of metastatic neuroendocrine gastroenteropancreatic tumors. Response rates were lower compared with those published in previous, nonrandomized studies. The antiproliferative effect of the tested substances was similar for functional and nonfunctional neuroendocrine tumors.

Supported in part by a grant from Ipsen Pharma, Ettlingen, and ESSEX Pharma, Munich, Germany.

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Related Correspondence

• Is Lanreotide and/or Interferon Alfa an Adequate Therapy for Neuroendocrine Tumors?
  Verena Völter and Christian Peschel
  JCO 2004 22: 573 [Full Text]
• Prospective, Randomized, Multicenter Trial on the Antiproliferative Effect of Lanreotide, Interferon Alfa, and Their Combination for Therapy of Metastatic Neuroendocrine Gastroenteropancreatic Tumors
  Nicola Fazio and Kjell Oberg
  JCO 2004 22: 573-574 [Full Text]

Related Reply

• In Reply:
  S. Faiss, U.-F. Pape, and B. Wiedenmann
  JCO 2004 22: 574-575 [Full Text]

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