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.
OBJECTIVE
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.


CONCLUSIONS
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.
Faiss
Siegbert
S
Universitätsklinikum Charité, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Augustenburger Platz 1, D-13353 Berlin, Germany.
Pape
Ulrich-Frank
UF
Böhmig
Michael
M
Dörffel
Yvonne
Y
Mansmann
Ulrich
U
Golder
Werner
W
Riecken
Ernst Otto
EO
Wiedenmann
Bertram
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000009:adverse effects; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D012016:Reference Values; D013004:Somatostatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D016019:Survival Analysis; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C060347:lanreotide; D013004:Somatostatin