Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics.
The advent of the 5HT(3) receptor antagonists (5HT(3) antagonists) in the 1990 s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase. 5HT(3) antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK(1) antagonists) belong to a new class of antiemetic agents that specifically target the NK(1) receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK(1) antagonists to dual therapy with a 5HT(3) antagonist plus dexamethasone improves the acute emesis protection by a further 10-15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20-30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled.
de Wit
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R
Department of Medical Oncology, Erasmus University Medical Center and Rotterdam Cancer Institute, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands. r.dewit@erasmusmc.nl
D000208:Acute Disease; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D003907:Dexamethasone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000627:therapeutic use*
D000932:Antiemetics; D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D012702:Serotonin Antagonists; D003907:Dexamethasone