Celio, L., Bonizzoni, E., De Braud, F., Agustoni, F., & Aapro, M. (2016). Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? Insight from the re-evaluation of two randomized studies. Supportive Care in Cancer, 24, 1025–1034.

To determine the effectiveness of dexamethasone against delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC)

This reanalysis consisted of of two cohorts of chemotherapy-naïve patients who were included in two phase 3, randomized, controlled trails investigating a dexamethasone-sparing regimen. Participants were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC and AC regimens. Patients were divided according to the effectiveness of prophylaxis against acute CINV as either high- (experienced neither vomiting nor moderate-to-severe nausea) or low-risk (experienced vomiting or moderate to severe CINV).

• N = 624 (237 received MEC and 380 received AC)  
• MEDIAN AGE RANGE = 50–60 years
• MALES: 50.4%, 45.5%, FEMALES: 49.6%, 54.5%
• KEY DISEASE CHARACTERISTICS: Various primary cancers; breast (380); solid tumors, colorectal, and lung most common
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy-naïve patients who were included in two randomized clinical studies investigating a dexamethasone-sparing regimen; received either MEC for a solid tumor or AC-containing chemotherapy for breast cancer

• SITE: Multi-site    
• SETTING TYPE: Outpatient

• PHASE OF CARE: Active antitumor treatment

Secondary analysis of two phase 3, randomized, controlled trials

• Patients used a daily diary for five days. Nausea was assessed using a Visual Analog Scale (VAS) or verbal category scale (no nausea; mild = did not interfere with normal daily life; moderate = interfered with normal daily life; and severe = required the patient to be bedridden).
• The primary efficacy endpoint was the proportion of patients with protection against both vomiting and moderate-to-severe nausea.
• The secondary endpoints were protection against delayed vomiting, protection against delayed moderate-to-severe nausea, duration of delayed symptoms (i.e., number of delayed days phase when patients experienced either vomiting or nausea), and maximum severity of delayed nausea (two or more out of the four days was considered severe). The patient’s satisfaction with antiemetic coverage was assessed on day 6 by a satisfaction VAS (a 100 mm line marked “not at all satisfied” at the left-hand end and “totally satisfied” at the right-hand end). 

• Low-risk patients who received MEC: There were no statistically significant differences between the one-day and three-day regimens.  
• Low-risk patients who received AC: The one-day regimen was significantly less effective than the three-day regimen.
• High-risk patients who received AC: The one-day regimen experienced less control than the three-day regimen (statistically significant for no full protection against chronic CINV and moderate-to-severe nausea alone). This improvement was of greater magnitude. Additional dexamethasone doses improved the protection rates against moderate-to-severe nausea on days 2 (p = 0.083), 3 (p = 0.003), and 4 (p = 0.024) postchemotherapy.
• There were no significant differences in the duration of delayed vomiting or nausea in patients receiving MEC who were at a high or low risk. 
• Acute vomiting was an independent predictor for delayed vomiting (p = 0.045), and acute moderate-to-severe nausea independently predicted delayed nausea (p = 0.0007).

The dexamethasone-sparing regimen (three-day) achieved excellent control of delayed symptoms in patients with no acute CINV and for low-risk patients receiving AC, but it was less effective in patients receiving HEC. Additional dexamethasone doses could be offered selectively.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Findings not generalizable
• Other limitations/explanation:  

Patients receiving AC regimens are at an increased risk of experiencing delayed CINV. Some patients might not benefit from a dexamethasone-sparing antiemetic regimen. In this study, the reduction of dexamethasone was less effective for patients at a high risk. Extending the use of dexamethasone could produce adverse effects, so selective dexamethasone prescriptions should be individualized.