Open‐label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron

Abstract

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval [CI]: −7.8%–12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

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

“…Aapro et al reported that a dexamethasone‐sparing regimen consisting of palonosetron plus single‐dose dexamethasone (d1 arm) would not be inferior to the same regimen followed by additional dexamethasone doses on days 2 to 3 after chemotherapy initiation (d3 arm) regarding complete response (CR; no emesis and no rescue medication) rate. Two subsequent randomized phase III studies were performed with a similar objective, which also showed the noninferiority of the dexamethasone d1 arm for the prevention of CINV in patients undergoing a broad range of MEC regimens . However, because of a wide range of noninferiority margin (15%) and limited number of subjects in these three studies, evidence for the noninferiority of the dexamethasone d1 arm in patients with risk factors for CINV is insufficient.…”

“…However, because of a wide range of noninferiority margin (15%) and limited number of subjects in these three studies, evidence for the noninferiority of the dexamethasone d1 arm in patients with risk factors for CINV is insufficient. In addition, it is unclear whether well‐known risk factors for CINV, such as female sex, younger age, and history of alcohol consumption , modify the treatment effect on the antiemetic outcome .…”

Cheaper Options in the Prevention of Chemotherapy-Induced Nausea and Vomiting

“…45 This study administered palonosetron 0.75 mg, which is the commonly used dose in Japan. Netupitant-palonosetron is a netupitant (an NK-1 antagonist) plus palonosetron combination that has recently been included in the NCCN guidelines.…”

Management of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Multiple-Day Highly or Moderately Emetogenic Chemotherapy: Role of Transdermal Granisetron

“…2011 ASCO guidelines recommended use of a two-drug combination of palonosetron (day 1 only) and dexamethasone (days 1-3) in patients receiving MEC; when palonosetron is not available, it may be substituted with a first-generation 5-HT 3 serotonin receptor antagonist, preferably granisetron or ondansetron [1]. Several randomized studies, however, showed that a regimen of palonosetron and single-day dexamethasone is noninferior to palonosetron plus dexamethasone for 2 or 3 days in controlling CINV induced by MEC chemotherapy [15][16][17]. These findings are reflected in the recommendations of the MASCC/ESMO Antiemetic Guideline 2016 [18]: for the prevention of acute nausea and vomiting in MECtreated patients, a 5-HT 3 receptor antagonist plus dexamethasone on day 1 is recommended, while the use of dexamethasone on days 2 and 3 can be considered in patients receiving MEC with well-known potential for delayed nausea and vomiting (such as oxaliplatin, anthracycline or cyclophosphamide).…”