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.

Summary Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 ig of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor a (TGF-a) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase IlIl trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy.

No abstract

Inhibin immunoreactivity was estimated in a number of gonadal and non-gonadal tumors. Dog Sertoli cell tumors and human granulosa cell and Leydig cell tumors contained high concentrations of inhibin-like material. Levels, comparable with those in normal testes and ovaries were detected in human testicular non-seminomas and in ovarian cystadenomas, thecomas and adenofibromas. No activity was found in human testicular Sertoli/Leydig cell tumors and seminomas and in ovarian adenocarcinomas, teratomas and a dysgerminoma. Furthermore, human adrenal cortical tissue (tumor and hyperplastic adrenal) contained inhibin immunoreactivity. No activity was found in human tumors of the stomach, gut, liver, kidney, pancreas and mammary gland or in meningiomas. It is concluded that inhibin is not a good marker for specific gonadal tumors. Inhibin might have intratumor actions as a growth or differentiation factor.

No abstract