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Drug Safety 1994-Sep

The risks and benefits of corticosteroids in advanced cancer.

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R Twycross

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Corticosteroids are extensively prescribed in advanced cancer for various specific indications (e.g. spinal cord compression), for pain relief, as hormone therapy and to stimulate appetite and wellbeing. Choice of corticosteroid is dictated largely by local fashion, and times of administration are more traditional than pharmacological. Corticosteroids have many potential disadvantages, some life-threatening (e.g. masked septicaemia). Others are seriously debilitating (e.g. myopathy, avascular bone necrosis). Oropharyngeal candidiasis is a common complication. Corticosteroids are withdrawn in about 5% of patients because of unacceptable adverse effects, including moon-face and diabetes mellitus. Corticosteroid hypersensitivity occurs, and the succinate salts have been associated with bronchospasm. Steroid pseudorheumatism may occur with high dose therapy or when tailing off after a prolonged course. Important drug interactions with corticosteroids relate to salt and water retention, and decreased glucose tolerance. Some anticonvulsants cause an increased clearance of corticosteroids and, with dexamethasone, up to a 50% reduction in the anticipated effect. The benefit of corticosteroids in terms of increased appetite, mood and activity has been demonstrated in several controlled trials. The effect may well be time-limited in most patients. In several studies, corticosteroids have resulted in an analgesic-sparing effect. Some centres use very high doses of dexamethasone in cases of spinal cord compression, although the justification for these is not obvious. Corticosteroids are used to help relieve nerve compression pain and in symptomatic raised intracranial pressure. Corticosteroids are also injected locally into or around bone metastases, particularly ribs and the sacro-iliac joints. Epidural injections are used for patients with troublesome intractable low back pain. Corticosteroids are now used less often in hypercalcaemia because of poor response rates. More benefit is obtained, however, if high dosages are used, e.g. prednisolone 60 to 80 mg/day. Dexamethasone is widely used as an antiemetic in association with chemotherapy. Some centres use dexamethasone by continuous subcutaneous infusion in selected patients when the oral route is not feasible. The choice of starting dose of a corticosteroid is largely arbitrary. It is important, however, not to miss a possible treatment benefit by prescribing too low a dose. For most patients, an initial dosage of prednisolone of 30 to 60 mg/day (dexamethasone 4 to 8 mg/day) is appropriate. In patients with anorexia, there are several alternative options that should be considered. There is evidence to suggest that patients with advanced cancer receiving a corticosteroid are not as closely monitored as other patients. There is a need to state clearly in writing the reason(s) for prescription and to review after 1 or 2 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

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