Endogenous cortisol exerts antiemetic effect similar to that of exogenous corticosteroids

Abstract

Summary Lower pre-chemotherapy night time cortisol excretion predicted more severe cisplatin induced nausea and vomiting in 42 ovarian cancer patients receiving ondansetron as a single antiemetic agent. Dexamethasone administration added to the antiemetic effect of ondansetron principally in patients who had low excretion of cortisol.Corticosteroids as single antiemetic agents have a well documented effect on mild to moderate chemotherapy induced emesis (Cassileth et al., 1983). During highly emetogenic chemotherapy, there is a synergistic antiemetic effect of corticosteroids and metoclopramide or 5-hydroxytryptamine (5-HT3) receptor antagonists (Kris et al., 1989;Smith et al., 1991). Recently we reported that nausea during chemotherapy with low emetic potential was inversely related to urinary cortisol excretion (Fredikson et al., 1992 Patients rated their nausea during the past 24 h at the morning of the first and second day after the cisplatin infusion by choosing one of four alternatives ranging from none to severe nausea. At the first morning patients also used a 100 mm visual analog scale (VAS) to report the severity of nausea. A zero score is anchored at the left end with 'no nausea at all' and a maximum score of 100 'worst possible nausea'. Emetic episodes (vomiting or retching) were recorded by patients during both days.In the statistical analyses patients responding with 'no' or 'mild' nausea were treated as one group and those responding 'moderate' or 'severe' nausea formed the other group. Regarding the emetic episodes, patients with complete or major response ( <2 emetic episodes) formed one group whereas minor response and failure (> 3 emetic episodes) formed the other group. A median split approach was used to form groups with relatively high and low cortisol excretion. Relative risk was used to describe the association between urinary cortisol levels and nausea and vomiting. Relative risk was calculated as the ratio between the proportions of patients with moderate or severe nausea, or > 3 emetic episodes in respective groups of interest. Calculation of 95% confidence intervals was performed as described by Greenland & Robins (1985). Student's t-test with one-tailed P-values was used to analyse VAS-ratings of nausea and the total number of emetic episodes. ResultsThe median used to form groups high and low in cortisol excretion was 23.2pmolmin-'. The high and low excretion group had a mean (standard error of the mean) of 38.7 (2.5) and 16.5 (0.9) pmol min-', respectively. The groups did not differ concerning the percentage of 1-vs 2-day chemotherapy course (chi2 = 0.12, P = 0.73). The mean cortisol excretion in patients receiving dexamethasone was 28.8 pmol min-' and in those receiving placebo 25.8 pmol min-' (t (40) = 0.68, P = 0.50). Evaluating the importance of age for the studied variables, patients were categorised by their median age (50 years). No significant association was found between patient's age, cortisol excretion, nausea intensity or emetic episodes (t (40)<1.12, chi2 (1)<0.54, ...

5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of chemotherapy-induced emesis

“…Corticoid metabolism is probably also involved in the pathophysiology of chemotherapy-induced emesis. Corticosteroids have shown a remarkable anti-emetic efficacy and a relationship between anti-emetic efficacy of corticosteroids and lower basal cortisol excretion has been reported (Hursti et al, 1993). The present data in carboplatin-treated female patients confirm these findings and indicate a close relationship between cortisol excretion levels and the risk of emesis.…”

“…The first group contains the type of cytostatics used, the combination of different drugs and the chemotherapy dose. The second group contains gender, age, history of alcohol intake, susceptibility for motion sickness, chemotherapy experience and biochemically measurable parameters such as noradrenaline (Fredrickson et al, 1994) and cortisol (Fredrickson et al, 1992;Hursti et al, 1993). However, methodological problems of the latter studies make it difficult to draw final conclusions regarding the relation between cortisol metabolism and emesis.…”

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

“…Recent research showed that nausea associated with chemotherapy is correlated with a reduction of plasma cortisol levels in cancer patients, which indicates an effect (direct or indirect) on the hypothalamic-pituitary-adrenal axis (Hursti et al, 1993;Morrow et al, 2002a). Studies in rat show elevated plasma cortisol levels with the production of CFA (Smotherman, 1985).…”

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting

“…Earlier studies have mainly investigated different corticosteroid quantities in comparison with no or placebo medication. Prior work in this area suggests that especially patients with low prechemotherapy night-time cortisol excretion profit from cortisol administration (Fredrickson et al, 1992), that endogenous cortisol exerts antiemetic effects similar to that of exogenous corticosteroids (Hursti et al, 1993), and dexamethasone in high doses (20 mg) may impair the control of delayed symptoms (Peterson et al, 1996) whereas this adverse effect was not observed at doses of 8 mg (Carmichael et al, 1994).…”