79 4 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING | PART TWO Effective approaches to reduce patients’ exposure to corticosteroids remain among the hot topics in clinical research on CINV. This is because the side effects of DEX may outweigh its benefits when used for CINV control. Patients receiving cumulative DEX doses may experience more severe side effects; recent prospective studies highlighted a potentially detrimental impact of short-term prophylactic dexamethasone in patients undergoing consecutive courses of emetogenic chemotherapy [27, 28]. The incidence of moderate to severe DEX-associated side effects in the present study was low compared with those reported in the study by Vardy et al [17]. These differences may be explained by inaccuracy of the DSQ to determine which side effects were caused by DEX given after chemotherapy, by the IV DEX given before chemotherapy, by the chemotherapy itself (45% of patients in the study by Vardy et al were treated with highly emetogenic AC combinations), or by other antiemetics or concomitant medications. Moreover, DEX-associated side effects in our study were only assessed after the first cycle of chemotherapy, while patients completed an average of four cycles in the study by Vardy et al. Thecurrent study shows that aDEX-sparingstrategywithondansetronandmetoclopramide ondays 2-3 is awell-tolerated alternative prophylactic treatment to control CINV afterMEC. Metoclopramide is a central D2-receptor antagonist with activity at the chemoreceptor trigger zone and vomiting center, but it also acts on peripheral D2, muscarinic, and 5-HT4 receptors to induce prokinetic activity. At higher doses of metoclopramide (2 mg/kg), 5-HT3 antagonist activity may also contribute to the antiemetic effect [29]. The daily dose of metoclopramide prescribed in this study (10 mg tid for two days) will not result in 5-HT3 antagonist activity. High doses of metoclopramide (e.g., 200 mg every 4–6hr) cause unacceptable extrapyramidal symptoms in more than 30% of patients [30]. Lower doses (25–50 mg) are associated with a very low incidence (<1%) of dyskinetic or extrapyramidal symptoms (31). The U.S. Food and Drug Administration issued a black box warning for metoclopramide, given the high risk of developing tardive dyskinesia if metoclopramide use extends beyond 12 weeks [32]. However, this concern does not apply to the short-term course of metoclopramide in our study, in which only two patients suffered from grade 4 involuntary movements of the oral and facial musculature. These patients recovered without sequalae, when metoclopramide was stopped. This study also demonstrates that the control of delayed CINV – and nausea in particular – remains suboptimal with current prophylactic strategies in patients receiving MEC. Regardless of the use of multiple-day DEX, TC in the delayed phase could not be achieved in almost 50% of patients. Only a minority of patients reported no nausea in the delayed and overall phase, andmore than one third of all patients needed rescue antiemetics in the delayed or overall phase. New drugs and new combinations of drugs may improve control of CINV in patients who are treated with MEC. A recent meta-analysis demonstrated a clear clinically significant benefit with the addition of a neurokinin-1 (NK1) receptor antagonist in carboplatin-based chemotherapy, but not for MEC regimens [33]. The atypical antipsychotic olanzapine, which acts on many different receptors, particularly the D2, 5-HT2c, and 5-HT3 receptors, has been established as a highly effective antiemetic for patients undergoing HEC or AC combinations [34, 35]. Results of the Korean South West Oncology Group (KSWOG) Study [36] showed that olanzapine in addition to palonosetron
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