Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial.
OBJECTIVE
The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure (progression, death, stop of study treatment) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut (mainly pancreatic) and midgut tumors.


METHODS
One hundred nine of 125 registered patients were randomized starting in January 1995, and 105 patients (51 monotherapy, 54 combination treatment) were finally analyzed in March 2000. Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging. Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not randomized because of stable disease.


RESULTS
Partial tumor regression occurred in 2.9%, 1.9%, and 5.7% and stabilization of tumor growth in 44.8%, 27.6%, and 15.2% at 3, 6, and 12 months, respectively, with no significant differences between both treatment arms. In March 2000, 9.5% of patients were in treatment. Time to treatment failure and long-term survival did not differ significantly between the 2 groups, with a median survival of 32 and 54 months for the octreotide and the combination groups, respectively. Survival was longer in patients not randomized because of stable disease (median, 68 months) and in those with low nuclear Ki-67. A trend toward longer survival was shown for patients with slow spontaneous tumor growth before randomization. Patients responding to treatment lived longer than unresponsive patients.


CONCLUSIONS
Combination treatment was not superior to monotherapy concerning progression-free and long-term survival. Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage.
Arnold
Rudolf
R
Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps University, Marburg, Germany. arnoldr@mailer.uni-marburg.de
Rinke
Anja
A
Klose
Klaus-Jochen
KJ
Müller
Hans-Helge
HH
Wied
Matthias
M
Zamzow
Karin
K
Schmidt
Christina
C
Schade-Brittinger
Carmen
C
Barth
Peter
P
Moll
Roland
R
Koller
Michael
M
Unterhalt
Michael
M
Hiddemann
Wolfgang
W
Schmidt-Lauber
Martin
M
Pavel
Marianne
M
Arnold
Christian N
CN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000627:therapeutic use*; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011788:Quality of Life
D000970:Antineoplastic Agents; D053379:Chromogranin A; D002864:Chromogranins; D016898:Interferon-alpha; D019394:Ki-67 Antigen; D006897:Hydroxyindoleacetic Acid; D015282:Octreotide