Hormonal treatment of advanced pancreatic cancer with LH-RH analogue (original) (raw)
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Gastroenteropancreatic endocrine tumors: Effect of Sandostatin® on tumor growth
Metabolism, 1992
One hundred fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumors entered a prospective multicenter trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumors, and five with other endocrine GEP tumors) to determine the efficacy of 200 pg Sandostatina three times a day in the control of tumor growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a "negative" selection of patients included in the trial and suggesting that Sandostatinm cannot prevent disease progress when it is far advanced. In the evaluation of 88 patients monitored for at least 3 months, partial regression was observed in 4.4%. stable disease in 50%. and tumor progression in 45%. However, an initially favorable response frequently occurred with a decrease in response later: 54.4% at 3 months to 38% at 12 months for the whole group of patients. Proven inhibition of tumor growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatina exerts a beneficial effect on tumor growth in patients with metastatic endocrine GEP tumors. This beneficial effect decreases with time and is as yet unpredictable in the individual patient.
World Journal of Surgery, 1993
A prospective study was performed to determine the efficacy of octreotide (Sandostatin| SMS 201-995) 200/rg 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 ail 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.
International Journal of Cancer, 1994
Nude mice bearing xenografts of the gastrin-responsive human gastric carcinoma MKN45 cell line were treated for 4 to 5 weeks with bombesin/gastrin-releasing-peptide(GRP) antagonist (RC-3095), somatostatin analogues RC-I60 and SMS 201 -995, or the combination of RC-3095 and RC-160. Tumor volumes and weights were reduced significantly to a similar extent by RC-I60 and SMS 20 1-995, administered by daily S. C. injections at a dose of 100 yg/day. Bombesin/GRP antagonist RC-3095, given S. C. at a dose of 20 &day, had the greatest inhibitory effect on tumor growth. The combination of RC-3095 with RC-160 did not further potentiate the suppression of tumor growth. Histologically, the number of mitotic cells decreased significantly in the groups treated with RC-I60 or the combination of RC-3095 with RC-160. Serum gastrin levels were significantly diminished in all treated groups. Therapy with RC-I60 or the combination also significantly decreased levels of serum growth hormone. Receptor assays on tumor membranes showed that bombesin was bound to 2 classes of receptor sites, one with high affinity and low capacity, the other with low affinity and high capacity. Binding sites for epidermal growth factor (EGF) were down-regulated in tumor cells after treatment with RC-3095, RC-160 or the combination of RC-3095 with RC-160. In studies in vitro, both RC-160 and RC-3095 significantly inhibited the proliferation of MKN45 cells in culture as measured by cell number. These data demonstrate, for the first time, that the growth of human gastric cancer in nude mice can be inhibited not only by somatostatin analogues, but also by administration of modern bombesin/GRP antagonists, such as o 1994 Wiley-Liss, 6zc.
British journal of cancer, 1991
The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT f...
Long-acting somatostatin analogues are an effective treatment for type 1 gastric carcinoid tumours
European Journal of Endocrinology, 2008
BackgroundGastric carcinoid tumours type 1 (GCA1) originate from hyperplastic enterochromaffin-like (ECL) cells secondary to hypergastrinaemia. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. We conducted a multicentre prospective study to assess the effects of long-acting SSA on hypergastrinaemia and ECL-cell proliferation in patients with GCA1.MethodsWe studied 15 patients with GCA1 treated with monthly long-acting release octreotide (LAR) (20–30 mg; n=14) or Lanreotide 90 mg (n=1) for at least 6 months. Patients had serum gastrin and chromogranin A measurements performed and biopsies taken from both tumours and surrounding mucosa before, and every 6–12 months following treatment. Sections were immunostained for neuroendocrine markers. The cell proliferation index Ki-67, intensity of staining before and after treatment and the degree of gastric wall invasion we...
Binding of gastrin(17) to human gastric carcinoma cell lines
Cancer research, 1988
The hormone gastrin stimulates acid secretion by gastric parietal cells and acts as a growth factor for the gastric mucosa. Gastrin receptors with dissociation constants of approximately 0.5 nM have been detected on isolated gastric parietal cells, and on some cell lines derived from colon carcinomas. We now report that gastrin is also bound by five cell lines derived from human gastric carcinomas, but that the affinities of these lines for gastrin range from 0.2 to 1.3 microM. Cholecystokinin8 binds to the cell line Okajima with an affinity similar to gastrin17, while shorter gastrin analogues bind with reduced affinity. Binding of gastrin is unaffected by acetylcholine, histamine, or a number of other hormones with the exception of insulin which inhibits binding with an IC50 value of 0.5 microM. The ability to bind gastrin with affinities in the microM range appears to be a property widespread among other tumor cell lines.
Growth responses of rat stomach cancer cells to gastro-entero-pancreatic hormones
International Journal of Cancer, 1982
Various hormones and peptides were added to rat stomach cancer cells growing in vitro in a serum-free medium and the cell number was determined by a spectro-photometric method. Five gastro-entero-pancreatic hormones or related peptides (tetragastrin, glucagon, secretin, cholecystokinin-pancreozymin and cerulein) significantly increased the number of stomach cancer cells from I50 % to 3 10 % of the number of control cells cultivated in a serum-free, hormone-free medium. On the other hand, insulin and vasoactive intestinal peptide, and other hormones (thyroxin, epinephrine, hydrocortisone, /3-estradiol. progesterone, testosterone), peptone broth and bovine serum albumin had no significant growth effect. All the active substances belong to the two major families of gastro-entero-pancreatic polypeptide hormones, suggesting the existence of hormone receptors at the surface of stomach cancer cells.
Effects of sandostatin and castration on pancreatic carcinogenesis in rats and hamsters
International Journal of Cancer, 1992
The effects of treatment with the somatostatin analogue Sandostatin, separately and in combination with surgical castration, on the development of azaserine-induced lesions in rat pancreas and N-nitrosobis(2-oxopropyl)amine (BOP)-induced lesions in hamster pancreas were investigated. The animals were divided in 4 groups and treated as follows: (a) controls, injected S.C. with saline solution (0.9% NaCI); (b) orchiectomy directly after the last treatment with carcinogen; (c) Sandostatin (SMS 20 1-995) subcutaneously; (d) orchiectomy followed by treatment with Sandostatin. No significant suppressive effects on plasma EGF or IGF-I concentrations were noted after Sandostatin treatment, but plasma gastrin levels decreased slightly in the rats, not in the hamsters. In rats, Sandostatin treatment enhanced rather than inhibited growth of acidophilic atypical acinar cell nodules. In hamster pancreas, by contrast, Sandostatin inhibited the development of putative pre-neoplastic ductular lesions. There was no interaction between treatment with Sandostatin and surgical castration. It was concluded that Sandostatin, when administered prophylactically, has an inhibitory effect on the growth of putative pre-neoplastic ductular, but not acinar, lesions.