Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma.
BACKGROUND
Malignant pancreatic endocrine tumors (PETs) have a poor prognosis and existing antitumor treatments are unsatisfactory. Recent studies have shown somatostatin analogues to have antitumor growth effects in patients with malignant PETs; however, to the authors' knowledge, little information exists regarding their efficacy or effect on survival in patients with progressive malignant gastrinoma, the most common symptomatic malignant PET. The purpose of the current study was to study prospectively the efficacy, safety, and effect on survival of long-term treatment with octreotide in consecutive patients with progressive malignant gastrinoma.


METHODS
Fifteen consecutive patients with malignant gastrinoma with progressive hepatic metastases were studied. All patients underwent conventional imaging studies (computed tomography scan, magnetic resonance imaging, ultrasound, and, if needed, selective angiography) and somatostatin receptor scintigraphy prior to treatment and at 3-6-month intervals while receiving treatment. The patients all were treated initially with octreotide, 200 microg every 12 hours, and at last follow-up were being maintained on long-acting release octreotide, 20-30 mg every month. Tumor size and/or number were used to classify patient responses as either no tumor response or tumor response (stabilization or decrease in size). Treatment response was correlated with tumor and clinical characteristics.


RESULTS
Tumors in 8 of the 15 patients studied (53%) responded at 3 months, with 47% (7 of 15 patients) demonstrating tumor stabilization and 6% (1 of 15 patients) demonstrating a decrease in tumor size. The mean duration of response was 25.0+/-6.1 months (range, 5.5-54.1 months). Six of the eight responders were continuing to respond at the time of last follow-up. Tumor response did not correlate with any clinical parameter (e.g., tumor extent, fasting gastrin, or acid secretory rates). However, slow-growing tumors were more likely to respond prior to treatment (86% vs. 0%) (P < 0.0014). During follow-up (range, 4-8 years), 25% of the responders died compared with 71% of the nonresponders, a difference that approached statistical significance (P = 0.10). Two patients (13%) developed serious side effects that required the withdrawal of octreotide.


CONCLUSIONS
Octreotide is an effective antitumor treatment in patients with progressive malignant gastrinoma. In approximately 50% of these patients octreotide has an antigrowth effect; treatment is associated with a low incidence of serious side effects compared with other antitumor treatments commonly used and, in contrast to many studies, the growth response is long-lasting. The results of the current study suggest that octreotide treatment should replace chemotherapy as the standard treatment for these patients, especially those patients with slow-growing tumors. Additional studies involving larger numbers of patients will be needed to determine a convincing effect on survival.
Shojamanesh
Homayoun
H
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA.
Gibril
Fathia
F
Louie
Adeline
A
Ojeaburu
Jeremiah V
JV
Bashir
Showkat
S
Abou-Saif
Alaa
A
Jensen
Robert T
RT
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015408:Gastrinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D005755:Gastrins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015282:Octreotide / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017481:Receptors, Somatostatin / Q000378:metabolism; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D005755:Gastrins; D017481:Receptors, Somatostatin; D015282:Octreotide