[Treatment of tumor therapy-induced nausea and vomiting].
ABSTRACT Even today, nausea and vomiting are two of the most distressing adverse effects associated with tumor therapy. The authors give an overview of the mechanism and the trigger factors (emetogenic potential of the chemotherapies, the patient risk factors, and the used antiemetic drugs) of nausea and vomiting. A short summary will describe the antiemetic drugs focusing on metoclopramide, steroid and the currently widely used setron therapy which is effective only during the acute phase of chemotherapy-induced nausea and vomiting (CINV). In the treatment of CINV the latest improvement was the introduction of the neurokinin (NK1) receptor antagonist class. Currently the only available agent is aprepitant which is indicated to treat CINV in case of highly and moderately emetogenic chemotherapies. The pivotal phase III trials defined that aprepitant is the first drug that is able to protect against the delayed phase of CINV plus can improve the antiemetic therapy during the acute phase. Currently aprepitant is reimbursed in Hungary only after the failure of setron therapy in case of high dose (\>50 mg/m2) cisplatin protocols. The authors give a recommendation how to treat CINV based on the latest international antiemetic guidelines.The mechanism and the trigger factors of radiotherapy-induced nausea and vomiting (RINV) are different from CINV. For treatment of RINV metoclopramide (due to reimbursement regulation) and ondansetron can be used. In case of radio-chemotherapy the antiemetic treatment should follow the CINV guidelines.
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ABSTRACT: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV). Patients receiving cisplatin > or = 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments. The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P <.001 for all three comparisons). Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.Journal of Clinical Oncology 11/2003; 21(22):4112-9. · 18.04 Impact Factor
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ABSTRACT: MDL 72222, the selective 5-hydroxytryptamine (5-HT) M-receptor antagonist, prevented or reduced cisplatin-induced emesis in ferrets. It is suggested that cisplatin-induced, and possibly other cytotoxic drug-induced vomiting may involve a 5-HT M-receptor mechanism.British Journal of Pharmacology 08/1986; 88(3):497-9. · 5.07 Impact Factor
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ABSTRACT: Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-groups, Phase III study. Patients with cancer who were scheduled to receive treatment with high-dose cisplatin chemotherapy were randomized to receive 1 of 2 treatment regimens; the standard therapy group received intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral dexamethasone 8 mg twice daily on Days 2-4. The aprepitant group received oral aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2-3; and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use of rescue therapy, and severity of nausea in a diary. A modified intent-to-treat approach was used to analyze the efficacy data. The primary endpoint was complete response (no emesis and no rescue therapy) during the 5-day period postcisplatin. Treatment comparisons were made using logistic regression models, and reported adverse events and physical and laboratory assessments were used to assess tolerability. A total of 523 patients were evaluated for efficacy, and 568 patients were evaluated for safety. During the 5 days after chemotherapy, the percentages of patients who achieved a complete response were 62.7% in the aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were 82.8% for the aprepitant group and 68.4% for the standard therapy group (P < 0.001); for Days 2-5, the complete response rates were 67.7% in the aprepitant group and 46.8% in the standard therapy group (P < 0.001). The overall incidence of adverse events was similar between the 2 treatment groups (72.8% in the aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group [207 of 285 patients]) as were rates of serious adverse events, discontinuations due to adverse events, and deaths. In patients with cancer who are receiving high-dose cisplatin-based chemotherapy, therapy consisting of aprepitant (125 mg on Day 1 and 80 mg on Days 2-3) plus a standard regimen of ondansetron and dexamethasone provided superior antiemetic protection compared with standard therapy alone and was generally well tolerated.Cancer 07/2003; 97(12):3090-8. · 5.20 Impact Factor