Review of the preclinical pharmacology and comparative efficacy of 5-hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis

Edith A. Perez

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Purpose: This analysis was undertaken to review published reports of the comparative efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in the prophylaxis of acute chemotherapy-induced emesis. Methods: Comparison data used are the preclinical pharmacology as well as the design and results of clinical trials. Seven comparative studies that used granisetron, ondansetron, or tropisetron in patients who received either moderately or highly emetogenic chemotherapy are reviewed. As the study designs, patient population, chemotherapy, antiemetic doses and schedule, and methods of assessment were slightly different, the results of each study are analyzed independently. Effectiveness is assessed by emetic episodes, nausea, and patient preference. Results: The preclinical pharmacologic profile is different among the 5-HT3 antagonists in terms of potency, selectivity, dose response, and duration of action. The comparative clinical trials show that a single intravenous (IV) dose of granisetron 3 mg is as effective as multiple (8 mg × 3) or single (32 mg) IV doses of ondansetron for the prevention of acute nausea and emesis due to cisplatin. In the two moderately emetogenic clinical trials, granisetron 3 mg IV was at least as effective as ondansetron 8 mg IV ± 24 mg orally and tropisetron 5 mg IV. Patient preference was evaluated in three of the four crossover trials: granisetron was preferred in three of four, and no preference was reported in the fourth. The one trial to compare ondansetron 0.15 mg/kg × 3 versus granisetron 10 μg/kg × 1 or granisetron 40 μg/kg IV demonstrated equivalent control of nausea and vomiting in patients who received cisplatin-based chemotherapy. Conclusion: The 5-HT3 receptor antagonists compared are highly effective antiemetic agents that have now become the standard of care for preventing chemotherapy-induced emesis. Whether the described preclinical differences among these agents are also clinically significant remains to be seen. In the comparative trials analyzed, the 5-HT3 receptor antagonists demonstrated relatively equivalent clinical efficacy. Cost analysis may favor the use of one agent over another depending on the emetogenic challenge, dose of the 5-HT3 antagonists, and number of doses recommended. Patient preference may be an important factor to be considered in future antiemetic trials.

Original languageEnglish (US)
Pages (from-to)1036-1043
Number of pages8
JournalJournal of Clinical Oncology
Volume13
Issue number4
StatePublished - Apr 1995

Fingerprint

Granisetron
Receptors, Serotonin, 5-HT3
Vomiting
Ondansetron
tropisetron
Pharmacology
Drug Therapy
Antiemetics
Patient Preference
Nausea
Serotonin Antagonists
Clinical Trials
Cisplatin
Emetics
Standard of Care
Cross-Over Studies
Appointments and Schedules
Safety
Costs and Cost Analysis
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Review of the preclinical pharmacology and comparative efficacy of 5-hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis. / Perez, Edith A.

In: Journal of Clinical Oncology, Vol. 13, No. 4, 04.1995, p. 1036-1043.

Research output: Contribution to journalArticle

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