Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy

Abstract

Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at -15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in Arms D3 and D1, respectively-were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK-RA and Palo in HEC.

One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis

“…In the present study, only the Kosaka study evaluated the efficacy of the dexamethasone‐sparing strategy in patients with breast cancer treated with AC and receiving three‐drug prophylaxis for CINV . Nevertheless, the study findings are consistent with the results of a recently published phase III trial that demonstrated a noninferiority difference between the three‐drug, dexamethasone‐sparing regimen and the control arm for the prevention of CINV caused by HEC regimens . Approximately 400 patients were included in the study, but the majority (77%) of them were patients with breast cancer treated with AC.…”

Pneumocystis jirovecii in a patient on dose‐dense chemotherapy for early breast cancer

“…A four-drug combination of an NK 1 receptor antagonist, a 5-HT 3 receptor antagonist, dexamethasone, and olanzapine should be used, with olanzapine continued on Days 2-4 MASCC-ESMO [11] In women with breast cancer, a three-drug regimen, including single doses of a 5-HT3 receptor antagonist, dexamethasone, and an NK 1 receptor antagonist (aprepitant, fosaprepitant, netupitant or rolapitant), given before chemotherapy is recommended If fosaprepitant, netupitant, or rolapitant has been used on Day 1, no additional dexamethasone is required on subsequent days NCCN [12] When used with netupitant/palonosetron, use 12 mg dexamethasone on Day 1 and 8 mg on Days 2 and 3, although "emerging data and clinical practice suggests dexamethasone dose may be individualized" EviQ [13] Recommended supportive medication for ddAC: Akynzeo and 12 mg dexamethasone on Day 1 8 mg dexamethasone on Days 2-4 (June 2018 update: may be reduced or omitted at physicians' discretion) Day 1 only [15]. Further lending support to a dexamethasone-sparing regimen was the randomized double-blinded, placebo-controlled, Phase III study by Ito et al [16], which demonstrated the non-inferiority of a dexamethasone-sparing regimen over a 3-day regimen in patients receiving highly emetogenic chemotherapy (HEC), when given with palonosetron and aprepitant. The patient in this case report received 40 mg of dexamethasone every 2 weeks as CINV prophylaxis or 19 mg prednisone equivalents/day.…”

Risk factors for delayed chemotherapy-induced nausea and vomiting with low-emetic-risk chemotherapy: a prospective, observational, multicenter study

“…Ito et al suggested that administration of dexamethasone on days 1–3, compared to only day 1, reduces the incidences of nausea, anorexia, depression, and fatigue during the delayed phase. 23 Thus, in patients who develop acute CINV, dexamethasone may be useful in preventing nausea and anorexia in the delayed phase. However, because dexamethasone has several side effects, including insomnia, indigestion/epigastric discomfort, agitation, and increased appetite, 24 , 25 we need to be mindful of these side effects when using dexamethasone for delayed antiemetic prophylaxis.…”