The Severity and Pattern of Emesis following Different Cytotoxic Agents

Abstract

Different cytotoxic drugs induce different patterns of emesis. This is relevant to clinical practice since we often see in the medical literature oversimplifications in the recommendation for management of chemotherapy-induced emesis, so that the same guidelines are given for cisplatin and non-cisplatin-containing chemotherapy. In particular, cisplatin induces a biphasic pattern of emesis which is characterized by an acute immediate phase and a delayed phase. These two phases are clearly different, especially when cisplatin is given in short i.v. administration (e.g. over 20 min to 1 h) and in high doses (100–120 mg/m²). On the other hand, cyclophosphamide and carboplatin induce a quite different pattern of emesis, characterized by a monophasic curve which, although more intense in the first 24 h, may continue for a number of days. The antiemetic response to 5-HT₃ receptor antagonists on days 2–5 is good in the case of carboplatin and cyclophosphamide and poor in the case of cisplatin (delayed emesis after cisplatin). This firmly suggests that the pathogenesis of cisplatin-induced emesis may differ from that induced by other cytotoxic drugs, especially in the delayed phase of emesis. We think that we should reserve the term ‘delayed emesis’ for the late emesis induced by cisplatin, while ‘prolonged emesis’ could be a better denomination for the late emesis induced by cyclophosphamide and carboplatin. The main clinical implication of these observations is that 5-HT₃ receptor antagonists should be administered over 3–5 days in the case of carboplatin and cyclophosphamide, while a short treatment during the first day could be sufficient to control the acute phase of cisplatin-induced emesis.

5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis

“…The current review has demonstrated that the clinical objective of preventing emesis will be achieved only when the 5-HT 3 ) concur that these agents should be given in combination with a corticosteroid to patients who are at high or moderate risk of developing emesis. These guidelines also provide a dosing guide for the use of 5-HT 3 receptor antagonists, although they are at variance with each other and with the recommendations laid out by the manufacturers.…”

Antiemetic efficacy of the neurokinin‐1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high‐dose cisplatin

“…This greater benefit with aprepitant may be due to the higher level of emetogenicity produced by combinations of chemotherapeutic agents, as well as by the mechanisms of emetogenicity of the concomitant agents themselves. Cyclophosphamide-induced vomiting, which occurs in a monophasic rather than biphasic pattern and produces a different profile of plasma serotonin levels and urinary excretion of 5-hydroxyindole acetic acid compared with cisplatin, 24,25 may be centrally mediated, possibly involving NK 1 receptors at which aprepitant exerts its antagonistic effect.…”

5-HT₃-Receptor Antagonists in the Management of Nausea and Vomiting in Cancer and Cancer Treatment

“…Delayed emesis starts at least 24 h after cancer therapy and may last for more than 5 days, with a peak incidence at around day 2–3 depending upon the agent [89,90,91,92] (fig. 3).…”