Abstract
The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes/no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P=0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response:54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P=0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapynonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P=0.024) and administration of rescue medication (P=0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P=0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.
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References
Andrews PLR, Howthorn J, Sanger GJ (1986) The effect of abdominal visceral nerve lesions and a novel 5-HT-M receptor antagonist on cytotoxic and radiation-induced emesis in the ferret. J Physiol 382:47P
Audhuy B, Cappelaeare P, Claverie N (1995) Double-blind comparative trial of the antiemetic efficacy of two i.v. doses of dolasetron mesilate (DM) and granisetron (G) after infusion with high-dose cisplatin chemotherapy (abstract). Eur J Cancer 31A [Suppl 5]:S253
Bigaud M, Elands J, Kastner PR, Bohnke RA, Emmert LW, Galvan M (1995) Pharmacology of the human metabolites of dolasetron, an antiemetic 5-HT3 receptor antagonist. Drug Dev Res 34:289–296
Chevallier B, Cappelaere P, Splinter T, Fabbro M, Wendling JL, Cals L, Clavel M, Giovannini M, Khayat D, Claverie N, Hahne W (1995) IV Dolasetron (DM) vs IV metoclopramide (M) in emesis prevention after cisplatin chemotherapy (CT) (abstract). Support Care Cancer 3:336
Conroy T, Cappelaere P, Fabbro M, et al (1994) Acute antiemetic efficacy and safety of dolasetron mesilate, a 5HT3 antagonist, in cancer patients treated with cisplatin. J Clin Oncol 17:97–102
Court-Brown WM (1953) Symptomatic disturbance of the single therapeutic dose of X-rays. Br Med J 1:802–804
Danjoux CE, Rider WD, Fitzpatrick PJ (1979) The acute radiation syndrome. A memorial to William Michael Court-Brown. Clin Radiol 30:581–584
Harman G, Omura G, Ryan K, et al (1996) A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis. Cancer Chemother Pharmacol (in press)
Kris MG, Grunberg SM, Gralla RJ, et al (1994) Dose-ranging evaluation of the serotonin antagonist dolasetron mesilate in patients receiving highdose cisplatin. J Clin Oncol 12:1045–1049
Miller RC, Galvan M, Gittos MW, Giersbergen PLM van, Moser PC, Fozard JR (1993) Pharmacological properties of dolasetron, a potent and selective antagonist at 5-HT3 receptors. Drug Dev Res 28:87–93
Plezia P, Modiano M, Alberts D, et al (1992) A double-blind, randomized, parallel study of two doses of intravenous (IV) MDL 73,147EF in patients (PTS) receiving high dose cisplatin (CPPD)-containing chemotherapy (abstract). Proc Am Soc Clin Oncol 11:407
Priestman TJ (1989) Clinical studies with ondansetron in the control of radiation induced emesis. Eur J Cancer Clin Oncol 25 [Suppl 1]:S29-S33
Priestman TJ, Priestman SG (1992) Clinical trials in the prevention and control of emesis induced by therapeutic radiation. Colloque Inserm 223:157–165
Priestman TJ, Roberts JT, Lucraft H, et al (1990) Results of a randomized double-blind, comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation. J Clin Oncol 2:71–75
Salazar OM, Rubin P, Keller B, Searantino C (1978) Systemic (half-body) radiation therapy: response and toxicity. Int J Radiat Oncol Biol Phys 4:937–950
Sorbe B, Berglind AM (1992) Tropisetron, a new 5-HT3 receptor antagonist in the prevention of radiationinduced nausea, vomiting, and diarrhoea. Drugs 43 [Suppl 2]:33–39
Young RW (1992) Mechanisms and treatment of radiation-induced nausea and vomiting. Colloque Inserm 223:157–165
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Bey, P., Wilkinson, P.M., Resbeut, M. et al. A double-blind, placebo-controlled trial of i.v. dolasetron mesilate in the prevention of radiotherapy-induced nausea and vomiting in cancer patients. Support Care Cancer 4, 378–383 (1996). https://doi.org/10.1007/BF01788845
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DOI: https://doi.org/10.1007/BF01788845