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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

European Institute of Oncology, Department of Medicine, Milan, Italy; Department of Internal Medicine, Uppsala University, Uppsala, Sweden

To the Editor:

The study by Faiss et al [1] comparing interferon, lanreotide, and their combination in patients with neuroendocrine carcinoma is interesting not least because of the lack of randomized trials in this area. However, we have several concerns.

First, it needs to be clarified whether the disease was re-evaluated by means of computed tomography (CT) alone, ultrasound alone, or both: the article states, "transabdominal ultrasound and CT scans" in the Methods, but "CT or transabdominal ultrasound" in the Results. Given the scarcity of responses to these therapies, and assuming WHO criteria [2] were used (which do not include ultrasound), this discrepancy should be explained. If "or" is true, WHO response evaluation criteria could not be used; if "and" is true, the reason for using both examinations should be explained.

Second, in the Discussion, the authors claim that the response was similar in the receptor-negative and receptor-positive patients. Seventy of 80 patients underwent 111-In octreotide scintigraphy, and 63 of 70 scans were positive; three of 22 in the lanreotide arm and four of 23 patients in the interferon arm were negative. Unfortunately, no description of the response of these patients is given in the Results, and it is not known whether the two patients who responded in the lanreotide and interferon arms were receptor-negative; in particular, it would be interesting to know whether receptor-negative patients responded to lanreotide rather than interferon. Furthermore, a tumor cannot be considered receptor-negative on the basis of octreoscan results alone.

Third, the authors do not discuss the one partially responding patient of the 11 who were switched to the combination. This is in line with the results of some previous studies [3,4], but needs to be addressed. Do the authors think it is a sign that the combination is better, or is the sequence better than the combination ab initio?

Finally, the interferon and combination treatments were not optimized, and the patients were heterogeneous. These two points also deserve comment in the Discussion.

We believe that some of the conclusions of this study are too hurried and need to be confirmed by additional trials.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Faiss S, Pape UF, Böhmig M, et al: 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. J Clin Oncol 21: 2689-2696, 2003[Abstract/Free Full Text]

2. World Health Organization: WHO Handbook for Reporting Results of Cancer Treatment. Geneva, Switzerland, World Health Organization, 1979, pp 22-27

3. Fjallskog ML, Sundin A, Westlin JE, et al: Treatment of malignant endocrine pancreatic tumors with a combination of alfa-interferon and somatostatin analogs. Med Oncol 19: 35-42, 2002[CrossRef][Medline]

4. Frank M, Klose K, Wied M, et al: Combination therapy with octreotide and alfa-interferon: Effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol 94: 1381-1387, 1999[Medline]

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Related Article

• 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, and Bertram Wiedenmann
  JCO 2003 21: 2689-2696 [Abstract] [Full Text]

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]

Related Reply

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

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