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Somatostatin analog Sandostatin and inhibition of tumor growth in patients with metastatic endocrine gastroenteropancreatic tumors

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Abstract

A prospective study was performed to determine the efficacy of octreotide (Sandostatin®; SMS 201–995) 200 μg tid in controlling tumor growth. The study included 21 patients with metastasized endocrine GEP tumors: 6 gastrinomas, 8 carcinoid syndromes, 7 nonfunctioning tumors. Treatment was performed for 3 to 59 months (median 15 months). Evaluation of the response to octreotide was facilitated in 12 patients by a pretreatment observation period of 3 to 47 months (median 17 months) during which the natural growth behavior was determined. Based on the presence or absence of a control period prior to treatment, 5 patients were considered to be responders, 7 as questionable responders (no pretreatment phase available), and 9 as nonresponders. None of the 21 patients had documented shrinkage of the tumor mass. The most favorable response was tumor standstill. In all but one responder an escape to an initially favorable response occurred after 6 to 28 months (median 14 months). Proved inhibition of growth was paralleled by a reduction of serum and urine hormone parameters, whereas unaltered progression of tumor growth was observed also in the presence of hormone suppression. Tumor growth and hormone release was inhibited in the absence and presence of somatostatin receptors on the tumor. It is concluded that octreotide exerts a limited effect on metastatic GEP tumor growth. The evaluation of a response to octreotide is facilitated by an observation period prior to the drug that provides information on growth characteristics of the tumor. The presence of octreotide receptors does not predict the success of therapy.

Résumé

Par une étude prospective chez 21 patients, on a déterminé l'efficacité de 200 μg de sandostatine (SMS 201–995) pour contrôler la croissance tumorale d'une tumeur endocrine du pancréas-GEP métastasée: 6 gastrinomes, 8 tumeurs carcinoïdes et 7 tumeurs non-fonctionnelles. Le traitement a été donné pendant une médiane de 15 (3–59) mois. La réponse au traitement a été comparée á l'évolution naturelle des tumeurs endocrines chez 12 de ces patients avant tout traitement pendant une médiane de 17 (3–47) mois. Selon qu'il y a eu une période d'observation avant le traitement ou pas, on a considéré 5 patients comme des “répondeurs possibles”, 7 comme des “répondeurs douteux” et 9 comme des “non répondeurs”. Chez aucun des patients, la tumeur n'a diminué de volume. La réponse la plus favorable a été une stabilisation de la croissance tumorale. Chez tous les “répondeurs” sauf un, une réponse initiale favorable s'est soldée par un échec après une médiane de 14 (6–28) mois. Parallèlement á l'inhibition de la croissance, on a observé une réduction hormonale dans le sang et dans les urines. La croissance tumorale n'a pas été altérée même en cas de suppression hormonale. La croissance tumorale et le largage hormonal n'ont pas été corrélés avec la présence ou l'absence de récepteurs de la somatostatine sur la tumeur. On conclut que la sandostatine exerce un effet tout á fait éphémère sur la croissance métastatique des tumeurs GEP. L'évaluation de la réponse au traitement a été grandement facilité par la période d'observation pré-traitement. La présence de récepeurs á la somatostatine ne prédit pas le succès de la thérapeutique par la sandostatine.

Resumen

Se emprendió un estudio prospectivo con el propósito de determinar la eficacia de 200 ug de sandostatina (SMS 201–995) tres veces al dia en el control del crecimiento tumoral. El estudio incluye 21 pacientes con tumor gastroenteropancreático (GEP) metastásicos: 6 gastrinomas, 8 sindromes carcinoides, 7 tumores no funcionantes. El tratamiento tuvo una duración de 3–59 meses (media 15 meses). La evaluación de la respuesta a la sandostatina se facilitó en 12 pacientes por un periodo de observación anterior al tratamiento de 3–47 meses (media 17 meses), del cual se dedujo el comportamiento natural de su crecimiento. Con base en la presencia o ausencia de un periodo de control anterior al tratamiento, 5 pacientes fueron calificados como de respuesta positiva, 7 como de respuesta cuestionable (no hubo fase pretratamiento disponible) y 9 como de respuesta negativa.

Ninguno de los 21 pacientes exhibió disminución de la masa tumoral. La respuesta mas favorable fué un estancamiento en el crecimiento del tumor. En todos los pacientes con respuesta positiva, menos en uno, se produjo un escape a una respuesta inicialmente favorable a los 6–28 meses (media 14 meses). La comprobada inhibición del crecimiento tumoral tuvo paralelismo en una reducción en los niveles séricos y urinarios de parámetros hormonales, en tanto que la inalterada progresión del crecimiento tumoral fue observada también en presencia de supresión hormonal. El crecimiento tumoral y la liberación hormonal fueron inhibidos tanto en ausencia como en presencia de receptores de somatostatina en el tumor.

Nuestra conclusión es que la sandostatina ejerce un efecto de corta duración sobre el crecimiento de tumores GEP metastásicos. La valoración de la respuesta a la sandostatina se facilita por un periodo de observación previo a la administración de sandostatina, el cual provee información sobre las caracteristicas del crecimiento del tumor. La presencia de receptores de somatostatina no es factor de predicción del éxito de la terapia con sandostatina.

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Authors and Affiliations

  1. Departments of Internal Medicine (Division of Gastroenterology and Metabolism) and Radiology, Philipps University, Marburg/Lahn, Germany

    Rudolf Arnold M.D., Christian Neuhaus M.D., Ralph Benning M.D., Wolf B. Schwerk M.D., Michael E. Trautmann M.D., Klaus Joseph M.D. & Christian Bruns M.D.

  2. Preclinical Research, Sandoz Ltd., Basel, Switzerland

    Rudolf Arnold M.D., Christian Neuhaus M.D., Ralph Benning M.D., Wolf B. Schwerk M.D., Michael E. Trautmann M.D., Klaus Joseph M.D. & Christian Bruns M.D.

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  1. Rudolf Arnold M.D.
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  2. Christian Neuhaus M.D.
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  3. Ralph Benning M.D.
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Arnold, R., Neuhaus, C., Benning, R. et al. Somatostatin analog Sandostatin and inhibition of tumor growth in patients with metastatic endocrine gastroenteropancreatic tumors. World J. Surg. 17, 511–519 (1993). https://doi.org/10.1007/BF01655111

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