The Difficult Trials

addition of the NK1-receptor antagonist, casopitant (day 1–3), to a combination of ondansetron (day 1–3) plus dexamethasone (day 1) was investigated in patients receiving moderately emetogenic chemotherapy [4]. In a subpopulation (n = 123) treated with oxaliplatin-based chemotherapy, the 0–120-h complete response rate (no emesis and no need for rescue antiemetics) was improved from approximately 70% to approximately 80% by addition of casopitant. The three studies strongly suggest that patients treated with oxaliplatin-based chemotherapy need antiemetic prophylaxis for both acute and delayed nausea and vomiting [2, 3]. A combination of a serotonin antagonist plus dexamethasone will provide sufficient antiemetic effect in the majority of patients [2–4], an effect that can be slightly improved by addition of the NK1-receptor antagonist casopitant [4]. In the Abbrederis study, 11 patients with refractory nausea and vomiting in course one seemed to benefit from the addition of the NK1-receptor antagonist, aprepitant, in subsequent cycles of the same chemotherapy. The small number of patients and the design of the study make more in-detail conclusions irrelevant. 2 other non-randomized studies have investigated aprepitant in patients with refractory nausea and vomiting [5, 6]. Both found that aprepitant optimized the antiemetic effect in patients receiving a combination of an anthracycline plus cyclophosphamide [5] and in patients receiving different regimens of moderately or highly emetogenic chemotherapy [6]. Randomized, double-blind studies have demonstrated that patients with refractory emesis in the first course of chemotherapy can benefit from the addition of an antiemetic with another mechanism of action in subsequent courses [7– 9]. For instance, the addition of the dopamine (D)2-receptor antagonist, metopimazine, improved the antiemetic effect of ondansetron [7] and of ondansetron plus methylprednisolone [8] in patients with refractory emesis. Furthermore, patients receiving moderately emetogenic chemotherapy and refracChemotherapy-induced nausea and vomiting are ranked by the patients as two of the most troublesome adverse effects. Consequently a large number of trials comparing different antiemetic regimens have been published during the past twenty years. The vast majority of these trials have included patients receiving their first course of cisplatin-based or cyclophosphamide-anthracycline (AC)-based chemotherapy. Clinical guidelines are therefore very specific and the level of evidence is high, when recommendations for antiemetic prophylaxis are given in patients treated with cisplatinor AC-based chemotherapy [1]. The study by Abbrederis et al. [2], published in this issue of OnkOlOgie is interesting because it included patients with cancer of the gastrointestinal tract – a study population rarely addressed in antiemetic trials. Furthermore a sub-population of patients with refractory emesis (emesis in the previous course of chemotherapy) was investigated, Abbrederis and colleagues found that the majority of patients (85%) obtained adequate antiemetic protection in cycle 1 with a regimen including a serotonin (5-HT)3-receptor antagonist (day 1) plus dexamethasone (day 1–3). 15 out of 81 patients (18.5%) receiving low-dose cisplatin (< 50mg/m) suffered from nausea and vomiting, confirming the high emetic risk potential [1] of this regimen. Contrary to this, only 1 out of 25 patients (4%), receiving the new platinum compound, oxaliplatin, experienced acute (day 1) and delayed (day 2–5) nausea and vomiting. 2 other studies, until now published as abstracts only, investigated antiemetic efficacy in patients treated with oxaliplatin-based chemotherapy [3, 4]. In the first study in which patients did not receive antiemetics beyond day 1 of chemotherapy [3], Hesketh et al. reported that among patients treated with oxaliplatin (85–100 mg/m), 97% were completely protected from acute emesis, but that 51% of the patients vomited and/or needed rescue antiemetics in the delayed phase. In a randomized, double-blind phase II study the