58 PART TWO | CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING a significantly higher proportion of patients on aprepitant reported no vomiting in the overall phase compared to the control group (76.2% versus 62.1%, respectively, p < 0.001). In the post-hoc analysis of the non-AC MEC subgroup, statistically more patients in the aprepitant group compared to the control group reported no vomiting; in the acute phase 96.5% vs. 91.6%, respectively, p < 0.05; in the delayed phase 84.5% vs. 73.9%, respectively, p < 0.05; in the overall phase 83.2% vs. 71.3%, respectively, p < 0.05. In a double-blind, parallel group study by Hesketh et al [22], enrolling 707 patients receiving non-AC MEC (oxaliplatin) for colorectal cancer, the efficacy of single-dose casopitant was compared to placebo. All patients received ondansetron on days 1-3 plus dexamethasone on day 1, and were chemotherapy naïve. The primary endpoint in this study was the percentage of patients achieving CR (defined as no vomiting, no use of rescue medication) during the overall phase. There were no significant differences between both groups; 86% of the patients in the casopitant group vs. 85% in the placebo group achieved CR (p = 0.7273). There were also no significant differences between the casopitant and placebo group in the acute phase (97% vs. 96%, respectively, p = 0.4771) and in the delayed phase (86% vs. 85%, respectively, p = 0.7273). There was also no significant difference in severity of nausea between casopitant and placebo in all phases. Ninety-one female patients who were younger than 70 years, and received carboplatinbased chemotherapy for gynecological tumors, were randomized to aprepitant or placebo in a multicenter, double-blind, phase II trial [23]. All patients received granisetron and multi-day corticosteroids. Previous exposure to chemotherapy is unknown. The primary endpoint was CR (no vomiting, no rescue medication) during the overall phase. CR rates were not significantly different between aprepitant and placebo in the overall phase (62% vs. 52%, respectively, p = 0.33). There were also no significant differences in CR rates during the acute and delayed phases between aprepitant and placebo; 98% vs. 96%, respectively, and 62% vs. 52%, respectively). NEPA, a fixed-dose combination of netupitant and palonosetron In a multicenter, double-blind study by Gralla et al [24], the efficacy of a single dose of NEPA (oral fixed-dose combination of 300 mg netupitant and 0.50 mg palonosetron) was compared to oral aprepitant plus oral palonosetron 0.50 mg, in 412 patients treated with either HEC or non-ACMEC regimens for a broad range of tumors. Seventy-six percent of the patients received non-AC MEC, mainly carboplatin and oxaliplatin-based chemotherapy. In this study, the dose/schedule of oral dexamethasone was open-label and based on the emetogenicity of the chemotherapeutic regimen. All patients were chemotherapy-naïve. The study was designed to assess the safety of NEPA, but also to assess the efficacy of this antiemetic drug. Overall incidence, type and frequency of adverse events were comparable between the treatment groups. In the overall population, CR rates (no vomiting, no use of rescue medication) in the overall phase were similar in cycle 1 (81% in the NEPA group vs. 76% in the control arm). The reported control of nausea was comparable in both groups: 84%-92% across cycles for NEPA, and 81%-87% for the control group. For the non-AC MEC subgroup, CR rates across cycles were also comparable between the treatment groups: 80%-93% in the NEPA group, and 82%-89% in the control group.
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