Receptor Agonists With Palonosetron May Reduce Needed Dexamethasone Duration

Administering a neurokinin-1 receptor antagonist (NK₁-RA) with palonosetron plus dexamethasone reduces the number of dexamethasone doses necessary for successful antiemetic treatment among patients with cancer receiving highly emetogenic chemotherapy (HEC), according to a study published in the Journal of Clinical Oncology.¹

Dexamethasone is a mainstay treatment for chemotherapy-induced nausea and vomiting, but prolonged administration leads to adverse events (AEs) that may significantly reduce patient quality of life (QoL). Recent studies showed that combination therapy with novel antiemetic drugs can spare dexamethasone on days 2 and 3 during moderately emetogenic chemotherapy.

For this double-blinded phase 3 study, researchers randomly assigned 401 patients with malignant tumors receiving HEC to receive dexamethasone on day 1 and placebo on days 2 and 3 with an NK₁-RA and palonosetron (Arm D1), or dexamethasone on days 1 to 3 (Arm D3).

Patients completed a QoL questionnaire at baseline and after study completion, and also maintained a diary throughout 5 days to record the effectiveness of antiemetic therapy, the use of rescue medications, and any treatment-related AEs.

Of the 401 patients initially enrolled in the study, 396 were eligible for analysis.

Patients in Arm D1 had a complete response (CR) rate of 44.0% compared with 46.9% for patients in Arm D3 (95% CI, -12.6% to 6.8%; P = .007) overall.

The CR rates on day 1 (acute phase) were 63.3% vs 64.5% for patients in Arms D3 and D1, respectively (95% CI, −12.6% to 6.8%; P = .007). During days 2 to 5 (delayed phase), the CR rate was 56.6% vs 51.5% among patients in arms D3 and D1 (95% CI, −14.8% to 4.6%; P = .023), respectively.

The most frequently observed dexamethasone-related AEs were hot flushes and tremors on days 4 and 5 among patients in Arm D3. For patients in Arm D1, higher rates of anorexia, depression, and fatigue were reported on days 2 and 3. There were no significant differences in QoL between study arms.

Reference

1. Ito Y, Tsuda T, Minatogawa H, et al. 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. J Clin Oncol. 2018 Feb 14. doi: 10.1200/JCO.2017.74.4375 [Epub ahead of print]