Role of octreodite in the management of patients with cancer

Question: What is the role of octreotide in the management of patients with cancer? Perspectives: Octreotide has approval from the Therapeutic Products Directorate of Health Canada for the control of symptoms in patients with carcinoid tumours, vasoactive intestinal peptide (VIP)-secreting tumours, and acromegaly, and for the prevention of complications following pancreatic surgery and of bleeding from gastro-oesophageal varices. The long-acting suspension is indicated for acromegalic patients and for patients with carcinoid tumours or VIP-secreting tumours who are adequately controlled with octreotide administered subcutaneously. Octreotide has also been used in practice in patients with diarrhoea resulting from chemotherapy treatment, in patients with advanced breast and gastrointestinal cancers, and in terminally ill cancer patients suffering from bowel obstruction. The drug is used for many indications, and controversy exists regarding its efficacy for certain of those indications. With the potential for variability in practice in Ontario, the Systemic Treatment Disease Site Group (DSG) felt that a systematic review of the best available evidence on the topic of octreotide use in cancer patients would be useful. Outcomes: Outcomes of interest included tumour response, survival, symptom relief or control, and quality of life. Methodology: A systematic search of the MEDLINE (Ovid; 1966 through October 2002), CANCERLIT (Ovid; 1983 through October 2002), and Cochrane Library (Issue 4, 2002) databases was undertaken. Randomised controlled trials that compared octreotide with placebo, observation, or other treatment in the management of patients with cancer were eligible for inclusion in the systematic review of the evidence. Given the lack of randomised data, non-controlled reports of octreotide for patients with neuroendocrine tumours or chronic bowel obstruction were also considered. Results: The DSG found twenty-five randomised controlled trials (two reported as abstracts), two clinical practice guidelines, one systematic review, and eighteen non-randomised trials for inclusion in the systematic review of the evidence. Practice Guideline: Chemotherapy-Induced Diarrhoea Octreotide is recommended at a dose of 100 μg subcutaneously three times daily, escalating every 8 hours by 50-100 μg until the diarrhoea is controlled, to a maximum of 500 μg three times daily. Pancreatic Surgery Octreotide, administered at a dose of 100 μg subcutaneously three times daily starting 1 hour before surgery and continuing for 7 days, is recommended as part of standard management for patients undergoing pancreatic surgery. Symptoms Associated with Carcinoid Tumours Octreotide is recommended to control symptoms associated with carcinoid tumours. Because the mechanism of action and pathophysiology of other secretory neuroendocrine tumours are similar to those of carcinoid tumours, it is reasonable to recommend octreotide to control symptoms associated with secretory neuroendocrine tumours. It is suggested that octreotide be administered in a subcutaneous dose of 100 μg three times daily, or 200 μg twice daily, with an increase in the dose of 50-100 μg every 8 or 12 hours until symptom control is achieved. Inoperable Bowel Obstruction Attributable to Advanced Cancer The use of 300 μg octreotide daily by subcutaneous infusion may be considered for the purpose of reducing symptoms such as nausea, vomiting, and pain, or avoiding the need for a nasogastric tube. Antitumour Agent Octreotide cannot be recommended as an antitumour agent for the treatment of metastatic breast cancer, advanced pancreatic cancer, or asymptomatic colon cancer. Further studies in advanced breast, colon, or pancreatic cancer are unlikely to be productive unless a different formulation or dose schedule is anticipated to be more active. Qualifying Statements: Chernotherapy-Induced Diarrhoea For patient convenience, an alternative-albeit less effective-option is standard oral antidiarrhoeal agents in the usual approved doses (for example, 4 mg loperamide initially, then 2 mg after every unformed stool, to a maximum of 16 mg per day). If the diarrhoea has not substantially improved in 24 hours, or if the patient requires intravenous rehydration, then octreotide should be administered at the recommended doses. Pancreatic Surgery In three large, placebo-controlled double-blind randomised trials, significant decreases in serious complications (pancreatic fistula, abscess, and fluid collection) were observed in patients receiving octreotide. No differences in mortality following surgery was observed in any of the trials between the octreotide and placebo groups.