Abstract
Selective 5-HT3 antagonists have proven to be safe and effective for the prevention of chemotherapy-induced nausea and vomiting. Dolasetron is a new highly selective addition to this class of antiemetics that has been shown to have significant antiemetic activity in patients receiving cisplatin-containing regimens. This pilot study was designed to evaluate the antiemetic efficacy of dolasetron in cancer patients receiving doxorubicin and/or cyclophosphamide. This study used an openlabel, non-randomized design to evaluate the efficacy and safety of intravenous dolasetron in the prevention of emesis in patients receiving doxorubicin (25–75 mg/m2) and/or cyclophosphamide (400–1200 mg/m2). Sixty-nine patients received a single, intravenous dose of dolasetron over 15–20 min beginning 30 min prior to the start of chemotherapy. Dose levels of dolasetron studied were: 0.3, 0.6, 1.2, 1.8 and 2.4 mg/kg. Patients were monitored for emesis, nausea and adverse events for 24 h after the start of chemotherapy. Overall, 61% of patients experienced complete control of emesis. No significant trend towards increased antiemetic efficacy (P = 0.076) or nausea control with increasing dolasetron dose was noted, although the power to detect significant differences was limited by the small number of patients on the 0.3-mg/kg and 2.4-mg/kg dose levels. Age, gender, and type of chemotherapy were significant predictors of complete antiemetic control. Adverse events were generally mild and included headache, chills, light-headedness, fever, diarrhea, dizziness, and asymptomatic prolongation of ECG intervals. Intravenous dolasetron is safe and effective in the prevention of emesis induced by doxorubicin and/or cyclophosphamide.
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References
Baltzer L, Kris MG, Hinkley L, et al (1994) Reversible electrocardiographic interval prolongations following the specific serotonin antagonists ondansetron (OND) and dolasetron mesylate (DM): a possible drug class effect without sequelae? (abstract). Proc Am Soc Clin Oncol 13:433
Beck TM, Ciociola AA, Jones SE, et al (1993) Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. Ann Intern Med 118:407–413
Boeijinga PH, Galvan M, Baron BM, Dudley MW, Siegel BW, Slone AL (1992) Characterization of the novel 5-HT3 antagonists MDL 73147EF (dolasetron mesylate) and MDL 74156 in NG108-15 neuroblastoma x glioma cells. Eur J Pharmacol 219:9–13
Boxenbaum H, Gillespie T, Heck K, Hahne W (1992) Human dolasetron pharmacokinetics. I. Disposition following single-dose intravenous administration to normal male subjects. Biopharm Drug Dispos 13:693–701
Clark R, Tyson L, Frisone M (1985) A correlation of objective (OBJ) and subjective (SUBJ) parameters in assessing antiemetic regimens (AER). Oncol Nurs Forum 12 [Suppl]: 96
Conroy T, Cappelaere P, Fabbro M, et al (1994) Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist, in cancer patients treated with cisplatin. Am J Clin Oncol 17:97–102
Dixon R, Cramer M, Conway DW, et al (1995) Single-dose, placebo-controlled phase I study of oral dolasetron. Pharmacotherapy (in press)
Galvan M, Gittos MW, Miller RC, Moser PC, Giersbergen PLM van, Fozard JR (1992) Dolasetron mesilate (MDL 73147EF), a potent anti-emetic 5-HT3 receptor antagonist (abstract). Br J Pharmacol 107 [Suppl]:449P
Gittos MW, Fatmi M (1989) Potent 5HT3 antagonists incorporating a novel bridged pseudopelletierine ring system. Actual Chim Ther 16:187–189
Grunberg SM, Hesketh PJ (1993) Control of chemotherapy-induced emesis. N Engl J Med 329:1790–1796
Hesketh PJ, Gandara DR (1991) Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst 83:613–620
Hunt TL, Cramer M, Shah A, Stewart W, Benedict CR, Hahne WF (1995) A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers. J Clin Pharmacol 35:705–712
Kris MG, Gralla RJ, Clark RA, Tyson LB, Groshen S (1987) Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone: a double-blind, randomized trial. Cancer 60:2816–2822
Kris MG, Grunberg SM, Gralla RJ, et al (1994) Dose-ranging evaluation of the serotonin antagonist dolasetron mesylate in patients receiving highdose cisplatin. J Clin Oncol 12:1045–1049
Lifsey DS, Gralla RJ, Clark RA, Kline RC (1993) Electrocardiographic changes with serotonin antagonist antiemetics: rate of occurrence and clinical relevance (abstract). Proc Am Soc Clin Oncol 12:463
Miller RC, Galvan M, Gittos MW, Giersbergen PLM van, Moser PC, Fozard G (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 (CDDP)-containing chemotherapy (CT) (abstract). Proc Am Soc Clin Oncol 11:407
Williams PD, Cohen ML, Turk JA (1991) Electrocardiographic effects of zatosetron and ondansetron, two 5-HT3 receptor antagonists, in anesthetized dogs. Drug Dev Res 24:277–284
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Hesketh, P.J., Gandara, D.R., Hesketh, A.M. et al. Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide. Support Care Cancer 4, 141–146 (1996). https://doi.org/10.1007/BF01845763
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DOI: https://doi.org/10.1007/BF01845763