Dexamethasone-Sparing Antiemetic Regimen in Patients Receiving Highly Emetogenic Chemotherapy
In a Japanese phase III noninferiority trial reported in the Journal of Clinical Oncology, Ito et al found that dexamethasone could be spared on days 2 and 3 in an antiemetic regimen including the neurokinin-1 (NK1) receptor antagonist aprepitant and palonosetron in patients receiving highly emetogenic chemotherapy (HEC).
Study Details
In the double-blind trial, 396 patients scheduled to receive HEC (cisplatin ≥ 50 mg/m2 or anthracycline plus cyclophosphamide) were randomized to receive dexamethasone on days 1 to 3 (group D3, n = 196) or dexamethasone on day 1 and placebo on days 2 and 3 (group D1, n = 200) combined with an NK1 receptor antagonist and palonosetron. Palonosetron was given intravenously (IV) at 0.75 mg (the approved dosage in Japan) 30 minutes before the start of chemotherapy on day 1. Oral aprepitant at 125 mg or IV fosaprepitant at 150 mg was given 1 hour before the start of chemotherapy; patients who received oral aprepitant on day 1 received aprepitant at 80 mg on days 2 and 3. Patients in both groups received dexamethasone at 12 mg IV on day 1; those in group D3 received IV or oral dexamethasone at 8 mg on days 2 and 3, with those in group D1 receiving placebo.
The primary endpoint was complete response, defined as no emesis and no rescue medications during the overall phase (0–120 hours). The noninferiority margin was set at –15.0% for the lower bound of the confidence interval (CI).
Response Rates
Complete response rates during the overall period were 46.9% in group D3 vs 44.0% in group D1 (difference = –2.9%, 95% CI = –12.6% to 6.8%, P = .007 for noninferiority). Complete response rates were 63.3% vs 64.5% (95% CI for the difference = –8.1% to 10.6%, P < .001 for noninferiority) during the acute phase (0–24 hours) and 56.6% vs 51.5% (95% CI for difference = –14.8% to 4.6%, P = .023 for noninferiority) during the delayed phase (24–120 hours). Hot flushes and tremors were observed more frequently as dexamethasone-related adverse events on days 4 and 5 in group D3; anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in group D1.
The investigators concluded, “Antiemetic [dexamethasone] administration on days 2 and 3 can be spared when combined with [an NK1 receptor antagonist] and [palonosetron] in HEC.”
The study was supported in part by Nichi-Iko Pharmaceutical Co.
Takako Eguchi Nakajima, MD, PhD, of St. Marianna University School of Medicine, Kawasaki, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
