GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.

Hesketh, Paul J.; Murphy, William K.; Lester, Eric P.; Gandara, David R.; Khojasteh, Ali; Tapazoglou, Efstathios; Sartiano, George P.; White, Dougľas R.; Werner, Karel; Chubb, James M.

doi:10.1200/jco.1989.7.6.700

Cited by 93 publications

(19 citation statements)

References 27 publications

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al., 1988;Hesketh et al, 1989;Einhorn et al, 1990). In randomised studies it has been proven superior to both placebo (Cubeddu et al, 1990) and high dose metoclopramide (Marty et al, 1990) in controlling cisplatin induced emesis.

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confidence: 99%

Reduction of carboplatin induced emesis by ondansetron

Harvey

Evans²,

Mitchell³

et al. 1991

Br J Cancer

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al., 1988;Hesketh et al., 1989;Einhorn et al., 1990). In randomised studies it has been proven superior to both placebo (Cubeddu et al., 1990) and high dose metoclopramide (Marty et al., 1990) in controlling cisplatin induced emesis. In non-cisplatin containing chemotherapy regimens it has been shown superior to metoclopramide in four randomised studies (Schmoll, 1989;Kaasa et al., 1990).Vomiting after most chemotherapeutic agents tends to start within a couple of hours of treatment. The onset of vomiting after carboplatin, however, is often delayed for 6-1O h (Calvert et al., 1982) and there is no previous study of the effect of ondansetron on carboplatin induced vomiting. This paper reports our initial experience with ondansetron in patients treated with carboplatin, who had proven refractory to a previous aggressive antiemetic regimen. Patients and methods PatientsAdult patients receiving carboplatin chemotherapy were eligible for treatment with ondansetron if they had vomited three times or more in the first 24 h of the previous course of chemotherapy. However, patients were excluded if they had a severe concurrent illness other than neoplasia, had hepatic dysfunction other than due to metastases or were receiving any other antiemetic medication, including benzodiazepines.Twenty-three women with ovarian cancer receiving carboplatin alone (300-400 mg m-2) and two men with testicular germ cell tumours receiving carboplatin (300 mg m2) with

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confidence: 99%

Reduction of carboplatin induced emesis by ondansetron

Harvey

Evans²,

Mitchell³

et al. 1991

Br J Cancer

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“…1) [2] indicating that simpler treatment schedules may be just as effective as repeated doses or infusions. In support of this observation, a similar degree of emetic control was achieved when ondansetron was administered in doses of 0.15-0.18 mg/kg every 2, 4, 6 or 8 h for 3 doses [1,8,9]. The urinary excretion of 5-hydroxyindolacetic acid (5-H1AA), the main metabolite of 5-hydroxytryptamine (5-HT or serotonin), has also been shown to increase in the 4-to 6-hour period following cisplatin, indicating the likely depletion of 5-HT from the enterochromaffin cells within a few hours after cisplatin administration, in paral lel with the development of emesis [5].…”

Section: Introductionmentioning

confidence: 56%

The Effectiveness of a Single Intravenous Dose of Ondansetron

Brown¹,

Paes²,

Bryson³

et al. 1992

Oncology

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This paper reviews data from 3 randomised, double-blind, parallel-group studies carried out in patients receiving high-dose cisplatin chemotherapy (50-120 mg/m²). These comparative trials show that a single intravenous dose of ondansetron (8-32 mg) is as effective as the continuous infusion and intermittent dose regimens used in previous clinical trials (8 mg i.v. followed by a 1 mg/h infusion for 24 h and 0.15 mg/kg i.v. X 3). One of the studies, carried out in Europe, demonstrated that a single 8 mg i.v. dose was as effective as 32 mg given either as an 8 mg loading dose followed by an infusion or as a single intravenous dose of 32 mg before chemotherapy. A similar study conducted in the United States showed that a 32 mg i.v. single dose was significantly more effective than both the 8 mg i.v. dose and the intermittent dose schedule. This study used a prospective stratification based on the dose of cisplatin (50-70 mg/m² and ≥ 100 mg/m²). In both strata the 32 mg dose was superior. These results emphasise the importance of selecting the dose of ondansetron (8-32 mg) based on factors that predispose patients to emesis, e.g., female gender, patients with a history of chemotherapy or motion sickness and the dose of cisplatin. The ondansetron dosing regimen for patients receiving a highly-emetogenic chemotherapy (8-32 mg i.v. followed by 8 mg orally twice daily) is both simple and flexible.

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“…Alkoholabusus (>10()mg/d über Jahre) scheint eine protektive Wirkung gegen das DDPinduzierte Erbrechen zu besitzen [1,10]. In vielen Fällen nehmen Nausea und Emesis bei Folgezyklen der Chemothera pie zu und sind bei Zw'eit-Chemotherapien schwieriger zu beherrschen als bei Ersttherapien [18,24].…”

Section: Introductionunclassified

Therapierefraktäre Emesis unter Cisplatin

et al. 1990

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Emesis unter Cisplatin (DPP)-haltiger Chemotherapie ist ein noch ungelöstes Problem und führt in bis zu 10% der Fälle zum Abbruch einer potentiell kurativen Therapie. Wir untersuchten die antiemetische Wirksamkeit des selektiven Serotonin (5HT₃)-Rezeptor-Antagonisten Ondansetron (GR 38032F, Glaxo) bei Patientinnen, die hochdosierte Platintherapie erhielten und unter einer Antiemetikatherapie mit Metoclopramid (MCP) an therapierefraktärem Erbrechen litten. Die Wirksamkeit bei akuter Emesis und bei verzögerter Emesis nach Platintherapie, sowie das Toxizitätsprofil der Prüfsubstanz wurden untersucht. Bei insgesamt 34 Therapiekursen einer Platin-Kombinationstherapie fanden wir bei 56% der Zyklen eine gute antiemetische Wirksamkeit. Nach 32 von 34 Therapiekursen (94%) gaben die Patientinnen unter Ondansetron eine subjektiv verbesserte Verträglichkeit der Chemotherapie im Vergleich zur vorhergehenden Antiemetikatherapie an. Die Nebenwirkungen unter Ondansetron waren zumeist leichter Natur und erforderten keine therapeutischen Interventionen. Am häufigsten traten Kopfschmerzen, Obstipation, Mund-trockenheit, Völlegefühl und ein asymptomatischer, transienter Transaminasenanstieg auf. Bei einer Patientin mit Peritonealkarzinose wurde nach der Therapie mit Ondansetron ein Ileus beobachtet.

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GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.

Cited by 93 publications

References 27 publications

Reduction of carboplatin induced emesis by ondansetron

Reduction of carboplatin induced emesis by ondansetron

The Effectiveness of a Single Intravenous Dose of Ondansetron

Therapierefraktäre Emesis unter Cisplatin

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