Treatment of patients with metastatic pancreatic and gastrointestinal tumours with the somatostatin analogue Sandostatin: a phase II study including endocrine effects

Abstract

Summary Somatostatin analogues can suppress the secretion of some gastrointestinal hormones and growth factors involved in the growth regulation of gastrointestinal cancers and can inhibit the growth of experimental pancreatic tumours. Therefore, in a phase II study 34 patients with metastatic pancreatic (n = 14), colorectal (n = 16) and gastric cancer (n = 4) were treated with three daily subcutaneous injections of 100-200 lAg of the somatostatin analogue Sandostatin . All patients had an extensive tumour load and 13 were pretreated with chemotherapy. Before Sandostatin treatment the patients with pancreatic cancer showed a higher mean plasma concentration of GH (P<0.05) and a lower concentration of 'total' somatomedin-C (P < 0.005) compared with patients with colorectal cancer; there was no significant difference betwen these two groups in plasma levels of directly assayable somatomedin-C, EGF/TGF-a, insulin and prolactin. Within 3 days after start of treatment, somatomedin-C levels initially decreased (without a change in basal plasma GH levels), but returned to pretreatment levels within 4-13 weeks. Plasma insulin levels also were suppressed but only during the first 3-5 days of treatment. Plasma EGF-TGF-a levels increased significantly at day 5 of treatment only in the pancreatic cancer patients. Twenty-seven per ceht of the patients showed stable disease for 3-9 months, but most patients experienced subjective improvement in the absence of serious side-effects. However, the overall survival remained disappointing, emphasising the need for better treatment regimens.

Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae

“…All of these analogues have demonstrated antiproliferative activity in cell culture and xenograft studies (Singh et al, 1986;Qin et al, 1992;Radulovic et al, 1993;Stewart et al, 1994;van Eijck et al, 1994). Some studies have been carried out using octreotide in patients with advanced gastrointestinal cancer, although the results have been contradictory: three trials failed to demonstrate clinical response to treatment (Klijn et al, 1990;Krook et al, 1993;Palmer Smith et al, 1994). The first of these trials (Klijn et al, 1990), a phase II study of 34 patients with metastatic pancreatic and gastrointestinal malignancies treated with octreotide, showed no objective responses to treatment and most patients did not demonstrate disease stabilization.…”

“…Some studies have been carried out using octreotide in patients with advanced gastrointestinal cancer, although the results have been contradictory: three trials failed to demonstrate clinical response to treatment (Klijn et al, 1990;Krook et al, 1993;Palmer Smith et al, 1994). The first of these trials (Klijn et al, 1990), a phase II study of 34 patients with metastatic pancreatic and gastrointestinal malignancies treated with octreotide, showed no objective responses to treatment and most patients did not demonstrate disease stabilization. In the second study (Krook et al, 1993), 260 patients with advanced colorectal cancer were randomized to receive either octreotide, 150 jig three times daily, or best supportive care.…”

Microencapsulated octreotide pamoate in advanced gastrointestinal and pancreatic cancer: a phase I study

“…but it was of statistical significance only on day 57 (P < 0.05). Densitometric scanning of low-molecular-weight IGFBPs on the British Joumal of Cancer (1998) 78(1) (Dy et al, 1992 (Emermann et al, 1984;Klijn et al, 1990). The stel mean plasma levels of octreotide in cohorts 2 1 weeks) and 3 (160 mg every 2 weeks) until day steady state was not reached before terminating tion in the majority of the patients.…”

“…Clinical studies evaluating the anti-tumour effect of somatostatin analogues in non-endocrine abdominal cancers have reported conflicting results (Savage et al 1987: Klijn et al 1990: Friess et al 1993: Smith et al 1994. Cascinu et al 1995.…”

Prognostic value of somatostatin receptor subtype 2 expression in colorectal cancer

“…With respect to colon cancer, therapy with SS analogs has been generally disappointing in terms of both survival and disease stabilization in the majority of the reported trials performed randomly on patients affected by this tumor [5][6][7]. In only one study a significant advantage in terms of survival has been reported [8].…”