Triple treatment with octreotide, galanin and serotonin is a promising therapy for colorectal cancer.
In patients with colorectal cancer, low levels of colonic somatostatin, galanin and serotonin have been found. Based on these findings, the effects of triple treatment with octreotide (a somatostatin analogue), galanin and serotonin on colorectal cancer has been studied. Triple therapy was found to reduce the volume and weight of both rat and human colon carcinoma in xenografts, apparently by necrosis, but also by reducing proliferation and expression of epidermal growth factor of cancer cells, and also by inducing apoptosis. It has been suggested that tumour necrosis results from ischemia in the tumour caused by a reduction in the tumour blood flow, a consequence of reduced number of tumour-feeding blood vessels and by constricting of tumour feeding arterioles. The effects of treating rat colorectal cancer using single, double and triple therapy with octreotide, galanin and serotonin were studied. Of these substances, galanin alone achieved a significant reduction in tumour-feeding blood vessels. Single and double regimes had some effect, but were not nearly so successful as triple treatment. The optimum treatment dose of triple therapy lies between 40 and 80 microg/kg/day, smaller doses had no effect on the tumours at all, while larger doses had no additional effect. The optimal administration route is continuous i.p. infusion, for 14 days. Triple therapy gave no obvious side effects, and had equivalent anti-tumour and therapeutic efficacy as standard treatment with 5-fluorouracil/leucovorin. Although this treatment appears to be a promising option, clinical trials need be conducted to establish whether it can be beneficial in clinical use.
Division of Gastroenterology and Hepatology, Institution of Molecular and Clinical Medicine, University Hospital, Linköping, Sweden. magdy.el-salhy@imk.liu.se
Magdy
M
El-Salhy
D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D019004:Galanin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D012701:Serotonin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D012701:Serotonin; D019004:Galanin; D015282:Octreotide