Dexamethasone for the prophylaxis of radiation-induced emesis: a National Cancer Institute of Canada Clinical Trials Group phase III study

Kirkbride, Peter; Bezjak, Andrea; Pater, J; Zee, Benny; Wong, Ralph; Cross, P.; Gulavita, Sunil; Blood, Paul; Sun, Aixia; Dundas, George; Ganguly, Pradip; Lim, Joann; Chowdhury, Ajmain; Kumar, Satyam; Dar, A. Rashid

doi:10.1016/s1278-3218(00)00067-6

Cited by 15 publications

(21 citation statements)

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“…Sykes et al [51] found that emesis-related quality of life was higher in a group of 33 palliative radiated patients treated with 5TH 3 -receptor antagonists (30% experienced nausea) compared to a control group including 33 patients treated with corticosteroids (72% experienced nausea). Global quality of life did in our study differ between patients with and without nausea but did not differ between the groups in the study by Sykes et al, nor between a group including 75 patients irradiated over upper abdomen treated with corticosteroids (30% vomited or retched) compared to 76 patients receiving placebo pills (51% vomited or retched) [26]. Radiotherapy induced nausea is commonly considered to be less problematic than post chemotherapy nausea [42], but our results indicate that also nausea during radiotherapy may affect the patients' daily life in several negative ways.…”

Section: Discussioncontrasting

confidence: 69%

One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient

Enblom

Axelsson

Steineck

et al. 2008

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Objective To describe the prevalence of nausea and vomiting during radiotherapy and to compare quality of life, psychological and functional status in patients experiencing or not experiencing nausea.Materials and methods A cross-sectional selection of 368 cancer patients treated with radiotherapy answered a questionnaire (=93% answering rate) regarding nausea, vomiting, actual use of and interest in antiemetic treatment, quality of life and psychological and functional status during the preceding week of radiotherapy. Mean age was 60 years and 66% were women. Main results Nausea was experienced by 39% (145) and vomiting by 7% (28) of patients in general, by 63% in abdominal or pelvic fields and by 48% in head/neck/brain fields. Abdominal/pelvic field (Relative risk (RR) 2.0), age ≤40 years (RR 1.9) and previous nausea in other situations (RR 1.8) implied an increased risk for nausea. Antiemetics were used by 17% and 78% were interested in or wanted more information about acupuncture treatment against nausea. Of the 145 nauseous patients only 25% felt that antiemetics had helped them and 34% would have liked additional treatment, although the nausea intensity was mild in 72%. The nauseous patients reported lower well-being and quality of life, lower satisfaction with aspects of daily living and more frequent anxiety and depressed mood than the patients without nausea. Conclusions Of all patients undergoing radiotherapy, 39% experienced nausea and one third of them would have liked more treatment against the nausea. This study stresses the importance to identify and adequately treat patients with increased risk for nausea related to radiotherapy.

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Section: Discussioncontrasting

confidence: 69%

One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient

Enblom

Axelsson

Steineck

et al. 2008

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“…Radiotherapy was considered moderately emetogenic if it was delivered using a posterior field, with or without an anterior field, and it it included an area of at least 80 cm 2 (calculated from a posterior or an anterior beam's eye view) between the superior border of the 11th thoracic vertebral body and the inferior border of the 3rd lumbar vertebral body. This radiotherapy target definition is consistent with definitions found in phase iii randomized trials of rinv from the ncic Clinical Trials Group 10,11 and is considered moderately emetogenic in international antiemetic guidelines 1,2 . Patients were ineligible if they had received highly or moderately emetogenic chemotherapy or cranial radiotherapy during the 7 days before the day of radiotherapy commencement; if they had experienced nausea, retching, or vomiting during the 24 hours before the hour of radiotherapy commencement; if they were scheduled to receive chemotherapy or cranial radiotherapy during the 10 days after the day of radiotherapy completion; or if they were taking corticosteroids or other antiemetics.…”

Section: Patientssupporting

confidence: 72%

Aprepitant and Granisetron for the Prophylaxis of Radiotherapy-Induced Nausea and Vomiting after Moderately Emetogenic Radiotherapy for Bone Metastases: A Prospective Pilot Study

et al. 2014

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“…The synthetic glucocorticoid dexamethasone has been shown to increase resistance to chemotherapeutic drugs and radiation therapy in cells from solid cancer (8 -12). This finding is of particular clinical significance because exogenously applied dexamethasone is a routine pretreatment used to attenuate the side effects of chemotherapy or irradiation, such as nausea and emesis (13,14). In epithelial ovarian cancer, except from the rare Federation Internationale des Gynaecologistes et Obstetristes stage IA with histopathologic grading G 1 , all patients receive either an adjuvant or first-line platinum-based chemotherapy, in advanced stages combined with paclitaxel.…”

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confidence: 99%

Glucocorticoids Inhibit Cell Death in Ovarian Cancer and Up-regulate Caspase Inhibitor cIAP2

Runnebaum

Brüning

2005

Clinical Cancer Research

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Purpose: Almost all patients with epithelial ovarian cancer receive chemotherapy and, concurrently, the synthetic steroid hormone dexamethasone to alleviate the side effects. This study aims to test the impact of steroid hormones on the apoptosis of epithelial ovarian cancer cells and to identify its mediators. Experimental Design: Tumor cell lines from 19 patients with advanced epithelial ovarian cancer were analyzed for glucocorticoid receptor, estrogen receptor, progesterone receptor, and androgen receptor expression. Cells were incubated with corresponding steroid hormones at serumequivalent doses in hormone-depleted medium. Apoptosis was induced by application of tumor necrosis factor^related apoptosis-inducing ligand or staurosporine and determined by poly(ADPribose)polymerase cleavage and cell survival. Microarray with 8K cDNA chips including apoptosisrelevant genes was used to study genes regulated by glucocorticoids. Results: In cell culture, tumor necrosis factor^related apoptosis-inducing ligand^induced apoptosis in OV-MZ-30 and OV-MZ-31 cells was reduced after treatment with dexamethasone or cortisol, but not with estradiol, progesterone, or androstenedione. Microarray analysis revealed a 7-fold up-regulation of the caspase inhibitor cIAP2 by dexamethasone in OV-MZ-30 and OV-MZ-31 cells. cIAP2 up-regulation by glucocorticoids was confirmed by RT-PCR and Western blot analysis in OV-MZ-30, OV-MZ-31, OV-CAR3, and SK-OV-3 cells. Down-regulation of cIAP2 expression by small interfering RNA sensitized SK-OV-3 cells to apoptosis inducer staurosporine. Under clinical conditions, treatment with dexamethasone was associated with significant up-regulation of cIAP2 in the ascites cells. Conclusions: Activation of the glucocorticoid receptor in epithelial ovarian cancer cells caused an antiapoptotic effect associated with the enhanced cellular expression level of cIAP2. Dexamethasone pretreatment of epithelial ovarian cancer patients receiving apoptosis-inducing chemotherapy raises questions about a negative effect on antitumor efficacy.Plasma levels of steroid hormones such as estrogens, androgens, progesterone, and the cellular expression level of the corresponding hormone receptors can be factors promoting the development of several solid tumors including ovarian and breast cancer (1 -3). The expression of the estrogen receptor in breast cancer is a well-known example and its pharmacologic inhibition by (selective) antiestrogens is extensively studied for breast cancer treatment as well as for its prevention (4, 5). Less is known about the impact of steroid hormones on the development of ovarian cancer. Contradictory studies on hormone replacement therapy regarding ovarian cancer risk have been presented (6, 7).Besides sex hormone receptors, the glucocorticoid receptor is another steroid hormone receptor with an effect on cancer cells. The synthetic glucocorticoid dexamethasone has been shown to increase resistance to chemotherapeutic drugs and radiation therapy in cells from solid cancer (8 -12). Thi...

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Dexamethasone for the prophylaxis of radiation-induced emesis: a National Cancer Institute of Canada Clinical Trials Group phase III study

Cited by 15 publications

References 3 publications

One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient

One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient

Aprepitant and Granisetron for the Prophylaxis of Radiotherapy-Induced Nausea and Vomiting after Moderately Emetogenic Radiotherapy for Bone Metastases: A Prospective Pilot Study

Glucocorticoids Inhibit Cell Death in Ovarian Cancer and Up-regulate Caspase Inhibitor cIAP2

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