Corticosteroids in advanced cancer : Epidemiology, symptom relief and patient experiences

Abstract: Cortisol is the principal circulating glucocorticoid in man and has a wide variety of effects in the body. In advanced metastatic cancer, glucocorticoids are used to alleviate symptoms such as anorexia, poor strength and poor wellbeing. The mechanisms behind the symptom relieving effects are still unclear. The general aim of this thesis was to study endogenous cortisol in patients with advanced cancer and the usage and impact of exogenous corticosteroids in symptom relief. Based on previous findings of impaired control of chemotherapy-related delayed nausea and vomiting in patients receiving single high-doses of dexamethasone, the recovery of the HPA-axis after a single dose of dexamethasone was examined in 10 healthy volunteers and compared with the recovery in 5 patients with gynaecological cancer receiving 8 or 20 mg of dexamethasone in conjunction with platinum-based chemotherapy (paper I). Analyses of urinary cortisol levels showed no differences in the recovery between patients and volunteers, indicating that corticosteroid-induced impairment in the control of delayed nausea was not dependent on the suppression and recovery of the HPA-axis. In an explorative cross-sectional study, urinary cortisol levels were analysed in 23 patients with advanced predominantly gastrointestinal cancer who had rated symptom severity using EORTC QLQ C-30 (paper II). Significant correlations were found between levels of urinary cortisol and more pronounced appetite loss, fatigue and nausea/vomiting. The mean values of urinary cortisol were high, indicating a chronic stress condition in this patient group. Attitudes and practice among physicians regarding treatment with corticosteroids in advanced cancer were examined in two cross-sectional surveys (paper III). The first survey collected answers from 338 physicians. In the second survey, data from 1292 patients enrolled in palliative care were registered. Corticosteroids were used in more than 50 % of the cancer patients and with high response rates when treating appetite loss, nausea, fatigue or poor well-being. The positive response came within the first week and was perceived as persisting beyond four weeks. Few physicians had guidelines on the use of corticosteroids in advanced cancer. Attitudes and examined practice were generally in good agreement with existing evidence. Cortisol production and metabolism was analysed in 13 patients with advanced cancer using high performance liquid chromatography and gas liquid chromatography on 24-hour urine samples (paper IV). Symptom assessments were made with ESAS before and after five days of treatment with 4 mg of betamethasone. Normal cortisol production together with a metabolic shift from cortisone to cortisol in peripheral tissue was seen. This shift was more pronounced in patients with shorter survival, especially in those with an inferior response to corticosteroid treatment. The results support the view of a chronic stress condition and points towards possible interactions between the neuroendocrine system and the immune system in patients with advanced, metastatic cancer. In a prospective observational study, qualitative content analysis was used to study the existential impact of corticosteroid treatment in 10 patients with advanced metastatic cancer (paper V). The patients were interviewed before and after one week of treatment with four milligrams of betamethasone. Prior to treatment patients reported distressing symptoms, deterioration and diminished autonomy, symbolising threat and death. Corticosteroid treatment resulted in enhanced physical abilities and feelings of a more normalized life, symbolising health and hope. This transfer from threat to hope has important existential consequences in the end of life care and should be addressed when communicating goals of treatment and care with the patient and family.