THE PRESENCE OF SOMATOSTATIN RECEPTORS IN MALIGNANT NEUROENDOCRINE TUMOR-TISSUE PREDICTS RESPONSIVENESS TO OCTREOTIDE

In 77 percent of patients suffering from a malignant carcinoid syndrome, administration of the somatostatin analog, octreotide (SMS 201-995, Sandostatin(TM)) induced clinical improvement coupled with a decrease in 24-hour urinary 5-hydroxyindole acetic acid (5-HIAA). This finding prompted an evaluation to determine the correlation between the presence of somato-satin receptors in tumor tissue and the response to octreotide in patients with advanced, metastatic, neuroendocrine tumors. In tissues of 31 tumors (20 carcinoid, eight islet-cell carcinoma, three medullary thyroid carcinomas), the presence of somatostatin receptors was analyzed by binding of the somatostatin analog I-125-Tyr3-SMS 201-995 and autoradiography. Receptors were detected in 16 of 20 samples of carcinoid tissues; all but one patient with receptor-positive tumors improved clinically after treatment with octreotide, and the urine 5-HIAA level was reduced a median of 63 percent (range, 39-94 percent) compared to values before treatment. Of the receptor-negative carcinoid patients, only one showed clinical improvement, which was minimal, and there was a negligible reduction in 5-HIAA after octreotide therapy. All eight patients with metastatic islet-cell carcinomas were positive for somatostatin receptors. Symptomatic improvement and a > 50 percent decrease in the level of at least one of the pathologically elevated marker hormones was seen in all eight. None of the three patients with medullary carcinoma of the. thyroid had a decrease in calcitonin, and all three were initially somatostatin receptor-negative. We conclude that the presence of ''somatostatin receptors in malignant neuroendocrine tumor tissue appears, to correlate with the response to octreotide therapy. Analysis of somatostatin receptors in malignant neuroendocrine carcinoma tissue should be included in future prospective clinical trials of this synthetic peptide.