16 The development of first-generation serotonergic receptor antagonists (5-HT3 RA) in the 1990s effectively suppressed acute CINV (0-24 hr after chemotherapy) [52], particularly whenused in tandemwithdexamethasone [53, 54]. This combinationhas been regarded as the standard prophylaxis ever since; however, delayed CINV (24-120 hr after chemotherapy still remains difficult to control [46, 55]. Newer antiemetic agents, that is, neurokinin-1 receptor antagonist (NK1 RA) [56, 57] and the second-generation 5-HT3 RA palonosetron [58, 59], were both introduced in the 2000s and have been proven to be equally effective for both acute and delayed CINV. Drug and guideline development have focused on the degree of emetogenicity of a chemotherapy regimen: highly emetogenic chemotherapy drugs (CINV in at least 90% of patients after chemotherapy); moderately emetogenic (MEC) drugs (30-90%); low emetogenic (10-30%); andminimal emetogenicity (<10%) [60]. Most research has focused on preventing episodes of vomiting. Less is known about reducing nausea independent of vomiting [61], and many of the antiemetic agents currently available do little to relieve chemotherapy-induced nausea [62]. Practice guidelines from the Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (MASCC/ESMO) [63] and the American Society of Clinical Oncology (ASCO) [64] are available to help determine optimal prophylaxis and treatment of CINV. Table 2 summarizes specific recommendations from these guidelines for MEC regimens. For patients receivingMEC (e.g. doxorubicin, irinotecan, oxaliplatinand cyclophosphamide, the MASCC/ESMO and ASCO guidelines recommend a 2-drug combination of a 5-HT3 RA with dexamethasone for the prophylaxis of acute CINV. They have recommended dexamethasone on days 2 and 3 following chemotherapy for MEC agents that are known to cause delayed CINV, such as cyclophosphamide, doxorubicin, and oxaliplatin. Dexamethasone-sparing or dose-modification approaches may be applicable when a patient’s exposure to corticosteroids must be limited. Recent studies involving 5-HT3 and/ or NK1 RA combinations support the use of dexamethasone-sparing approaches (i.e. dexamethasone coadministration on day 1 only) [65-70]. However, several questions remain unanswered regarding the exact therapeutic impact of the dexamethasone-sparing strategy on the management of CINV. Specifically, how effective is this strategy compared with a multiple-day dexamethasone regimen against delayed CINV. It is also not sufficiently clear whether the effect is different when control of nausea is assessed, and what evidence exists for the efficacy of a dexamethasone-sparing strategy in combination with other active agents.
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