Originally published as JCO Early Release 10.1200/JCO.2009.22.8510 on August 24 2009

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Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group

From the Department of Internal Medicine, Division of Gastroenterology and Endocrinology; Institute of Medical Biometry and Epidemiology; Coordinating Centre for Clinical Trials (KKS); and Departments of Radiology and Pathology, Philipps University, Marburg; Department of Internal Medicine, Charité Medical School and Hospital (Virchow), Berlin; Department of Internal Medicine, University of Hamburg, Hamburg; and Department of Internal Medicine, University of Freiburg, Freiburg, Germany.

Corresponding author: Rudolf Arnold, MD, Wittelsbacherstr 6, 80469 München, Germany; e-mail: arnoldr{at}mailer.uni-marburg.de.

Purpose Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.

Patients and Methods Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.

Results Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18).

Conclusion Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.

Written on behalf of the PROMID Study Group and endorsed by the European Neuroendocrine Tumor Society.

Supported by grants from Novartis, Nürnberg, Germany.

Novartis participated in the development of the study design and provided the verum medication and funding, but did not participate in the collection, analysis, and interpretation of the data.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00171873 [ClinicalTrials.gov] .

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