Treatment with corticosteroids can control mild to moderate emesis during chemotherapy (Cassileth et al., 1983) and adds to the antiemetic effect of high-dose metoclopramide in severe emesis (Bruera et al., 1983). Moreover, pregnancy induced nausea is more common among women with low than high cortisol excretion (Jarnfelt-Samsioe et al., 1986). These findings warrant an investigation whether endogenous cortisol secretion is associated with nausea induced by chemotherapy.The aim of the present study was to relate endogenous cortisol secretion to individual differences in chemotherapy induced nausea and vomiting. Urinary cortisol excretion remain stable over time, particularly during resting conditions (Forsman & Lundberg, 1982). Therefore, night time urine was collected to assay cortisol excretion. Self-reports were used to assess nausea and vomiting. no nausea at all' and a maximum score of 100 denotes 'worst possible nausea'. Vomiting episodes were counted. Self-reports of nausea (VAS) and vomiting were given during (one report) and after (two reports) infusion on the treatment day. Patients also reported their nausea and vomiting every 6th hour for the 2 following days. The daily averages of these values are reported. Vomiting was excluded from further analyses because of its low occurrence.The median used to form groups high and low in cortisol excretion was 60.5 pmol min-'. The high and low excretion group had an average (s.e.m.) of 107.3 (10.8) and 31.4 (5.7) pmol min-' respectively. Figure 1 shows that the group with high compared to low night-time cortisol excretion experienced significantly less nausea.Nausea was higher in patients with relatively lower cortisol levels during (t(18) = 2.55; P<.02) and after (t(18) = 3.01; P <.01) the chemotherapy infusion as well as on the first (t(18) = 2.47; <,.02) and second (t(18) = 2.77; <.01) day after treatment. The group with low excretion rates was younger (45.2; s.e.m. = 2.5) than the group with high excretion (56.1; s.e.m. = 3.3) (t(18) = 2.66; <.02). Using a median split defined by age, the average level (s.e.m.) of nausea during the treatment day was 12.1 (5.4) in young patients and 4.9 (2.8) in older ones (t(18) = 1.18; n.s.). Averaged over post-treatment days 1 and 2 nausea was 22.1 (8.0) and 12.0
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, ...
To understand the relation between fatigue and patients emotional situation at the end of life, this cross-sectional study aimed to explore the association between multidimensional aspects of fatigue, emotional functioning and quality of life (QoL) in patients with advanced cancer at the end of life. Patients with advanced cancer answered fatigue related measurements (Borg Category Ratio-10 scale, Multidimensional Fatigue Inventory-20, Swedish Occupational Fatigue Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30), when admitted for specialised palliative care. A total of 228 patients with a median length of survival of 63 days were included. In relation to time of survival, fatigue increased closer to death, in both global and multidimensional aspects, as well as the patient's experience of being sleepy. Marital status was found to affect the experience of fatigue in both global and multidimensional ratings of fatigue. The association between the experience of fatigue and feelings of being tense, worried, irritable or depressed and rated QoL decreased and was not evident closer to death. Fatigue in all dimensions increased, as patients got closer to death. The association between fatigue and both QoL and negative emotions faded away during the last days and weeks of life.
The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.
The participants in the day care group and the comparison group reported similar levels of perceived functioning and symptoms, as measured by the EORTC QLQ-30, with no significant differences between the groups. However, the day care group reported higher levels of emotional well-being as measured by the MACL than the comparison group reported, although these differences were not statistically significant.
Summary We investigated how residual tumour burden after cytoreductive surgery was related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian cancer patients receiving their first chemotherapy course. The anti-emetic treatment included ondansetron combined with dexamethasone or placebo. After chemotherapy all patients received ondansetron only for 5 days. Two categories of tumour burden (TB) were formed according to the diameter of the greatest residual tumour (<2 cm = minimal TB and > 2 cm= large TB). Self-reports of nausea and vomiting were obtained for 15 days. Other potential predictor variables were assessed and included in multivariate analyses. Patients with large compared with minimal TB had more delayed emesis, especially on days 2-7. They also had more acute nausea. The aggravating effect associated with large residual TB was more evident in patients >55 years. During the second week after the chemotherapy the occurrence of nausea was higher in patients >55 years than in those <55 years. This was seen primarily in patients with large residual TB. Predictors for no delayed emesis at all were anti-emetic treatment with dexamethasone, minimal tumour burden, low neuroticism and no history of motion sickness. The increased risk of 'persistent' delayed nausea and vomiting seen in older patients with large tumour burden may have important clinical implications and warrants further attention.
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