Fausto Roila, MD
For the prevention of nausea and vomiting after the first day of cisplatin-based chemotherapy, both aprepitant and metoclopramide when used in combination with dexamethasone were found to be similarly effective, according to findings of a randomized, double-blind trial presented at the MASCC-ISOO 2014 International Symposium.
Aprepitant is a P/neurokinin 1 receptor antagonist, which, when administered with dexamethasone, is the current recommendation for the treatment of cisplatin-induced nausea and vomiting during both the acute (ie, within the first 24 hours) and delayed (ie, after the first 24 hours) phases of treatment, noted the study’s lead author, Fausto Roila, MD, from the Department of Medical Oncology at S. Maria Hospital, in Terni, Italy.
The trial reported here was designed to determine whether aprepitant plus dexamethasone (A+D) would be superior to metoclopramide plus dexamethasone (M+D) in the prevention of cisplatin-induced emesis in the delayed setting among cancer patients who had been given the recommended aprepitant regimen on day 1.
Patients were included in the trial if they were chemotherapy naïve and scheduled to receive cisplatin chemotherapy at doses of 50 mg/m2
or greater. Prior to chemotherapy, all patients had received intravenous palonosetron (0.25 mg), dexamethasone (12 mg), and oral aprepitant (125 mg).
The primary endpoint was complete response rate
, defined as no vomiting, and no rescue treatment, from days 2 through 5 after chemotherapy. A superiority study was planned, with the hypothesis being that aprepitant plus dexamethasone would increase by 12% the complete response in delayed emesis (from 65% to 77%). Due to accrual difficulties, however, the study was closed before reaching the dimensions fixed in the protocol.
A total of 303 patients were enrolled in the trial, of whom 284 patients were fully evaluated (n=147 and n=137 in the A+D and M+D arms, respectively). Patients in both cohorts received 8 mg daily dexamethasone on days 2 to 4; patients in the A+D arm also received aprepritant (80 mg daily) on days 2 to 3, and those in the M+D arm received metoclopramide (20 mg/4 times daily) on days 2 to 4.
For the clinical assessment, patients reported the presence, intensity, and duration of nausea, as well as the frequency of vomiting episodes, adverse events, and any rescue treatments via a diary card filled out each day on days 1 to 6. They also completed the Functional Living Index-Emesis (FLIE) at baseline and on day 6.
“In the first 24 hours, when patients received the same antiemetic prophylaxis, the results are similar,” said Roila, with both combinations demonstrating a >94% response. When results of the combinations for days 2 to 5 were analyzed, he continued, complete responses were also not significantly different between the aprepitant (80.3%) and metoclopramide (82.5%) cohorts (P
More patients in the metoclopramide arm (84.7%) had metastatic disease than did patients in the aprepitant arm (73.5%; P
<0.03). Roila noted, however, that after adjusting for this characteristic (using logistic linear models), no significant difference between the two treatments emerged.
The percentage of patients with no nausea and no vomiting on days 2 through 5 were similar and not significantly different between the treatment groups, and there were no significant quality-of-life differences between the treatment groups in the impact of nausea and vomiting as measured by responses to the FLIE questionnaire.
Adverse events in the delayed phase were also not significantly different between the aprepitant and metoclopramide groups, the most frequent of which were asthenia (23.8% vs 23.4%, respectively), hiccup (16.1% vs 19%), and constipation (11.6% and 10.9%).
An important limitation of the study, said Rolia, was the fact that it was of a lower power than planned (55% in lieu of the planned 80%). Roila said he believed the results to be sufficiently reliable, however, noting that typically, the difference between treatments in antiemetic studies is fixed at 15% in lieu of 12%, and if so, the power of the current study would have been 76%, which is close to the 80% convention.
Roila F, Ballatori E, Ruggeri B, et al. Aprepitant versus metoclopramide, both combined with dexamethasone, for preventing cisplatin-induced delayed emesis: a randomized, double-blind study. Presented at: MASCC/ISOO International Symposium on Supportive Care in Cancer; June 26-28, 2014; Miami, Florida. Abstract 0083.
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