BACKGROUND: For the prevention of chemotherapy-induced nausea and vomiting (CINV) during the delayed phase (24-120 hr) after moderately emetogenic chemotherapy (MEC), the use of 3-day dexamethasone (DEX) is often recommended. This study compared the efficacy and safety of two DEX-sparing regimens with 3-day DEX, focusing on delayed nausea. PATIENTS AND METHODS: This open-label, randomized, phase III study was designed to demonstrate noninferiority of two DEX-sparing regimens: ondansetron + DEX on day 1, metoclopramide on days 2-3 (MCP arm), and palonosetron + DEX on day 1 (PAL arm) to ondansetron on day 1 + DEX on days 1-3 (DEX arm) in chemotherapy-naïve patients receiving MEC. Primary efficacy endpoint was total control (TC; no emetic episodes, no use of rescue medication, no nausea) in the delayed phase. Noninferiority was defined as a lower 95% CI greater than the noninferiority margin set at -20%. Secondary endpoints included no vomiting, no rescue medication, no (significant) nausea, impact of CINV on quality of life, antiemetics-associated side-effects. RESULTS: Treatment arms were comparable for 189 patients analyzed: predominantly male (55.7%); median age 65.0 years; colorectal cancer (85.7%); oxaliplatin-based chemotherapy (81.5%). MCP demonstrated noninferiority to DEX for delayed TC [MCP 56.1% versus DEX 50.0%, 95% CI (-11.3%, 23.5%)]. PAL also demonstrated noninferiority to DEX [PAL 55.6% versus DEX 50.0%, 95% CI (-12.0%, 23.2%)]. There were no statistically significant differences for all secondary endpoints between treatment arms. CONCLUSION: This study showed that DEX-sparing regimens are noninferior to multiple-day DEX in terms of delayed TC rate in patients undergoing MEC. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number: NCT02135510). IMPLICATIONS FOR PRACTICE: Chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24-120 hr post-chemotherapy) remains one of the most troublesome adverse effects associated with cancer treatment. In particular, delayed nausea is often poorly controlled. The role of dexamethasone (DEX) in the prevention of delayed nausea after moderately emetogenic chemotherapy (MEC) is controversial. Our study is the first to include nausea assessment as a part of the primary study outcome to better gauge the effectiveness of CINV control and patients' experience. We show that a DEX-sparing strategy does not result in any significant loss of overall antiemetic control: DEX-sparing strategies incorporating palonosetron or multiple-day metoclopramide are safe and at least as effective as standard treatment with a 3-day DEX regimen with ondansetron in controlling delayed CINV - and nausea in particular - following MEC.
Metoclopramide, Dexamethasone or Palonosetron for Prevention of Delayed Chemotherapy-induced Nausea and Vomiting after Moderately Emetogenic Chemotherapy (MEDEA): a Randomized, Phase III, Noninferiority Trial