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With the advent of newer antiemetic agents, is dexamethasone still a necessary part of antiemetic prophylaxis for patients with breast and other cancers on highly emetogenic chemotherapy (HEC)?

Venkatraman Radhakrishnan, DM, of the Adyar Cancer Institute in Chennai, India, and colleagues explored that question in a randomized clinical trial (RCT). "To date, to our knowledge, there have been no published RCTs on chemotherapy-induced nausea and vomiting prophylaxis regimens for HEC omitting dexamethasone," the researchers noted in .

The trial included 346 chemotherapy-naive patients who received single-day HEC and were randomized to a dexamethasone (DEX)-free prophylaxis regimen (olanzapine, palonosetron, and fosaprepitant) or dexamethasone with olanzapine and palonosetron. The majority of participants, more than 60%, were patients with breast cancer. Patients with lung, head and neck, and other cancers were also included.

"To our knowledge, in our manuscript, we present the findings of the first blinded phase III RCT demonstrating the efficacy of a DEX-free antiemetic prophylaxis regimen in the era of newer antiemetics, such as the NK-1 receptor antagonists, 5-HT3 receptor antagonists, and olanzapine," the team said.

Radhakrishnan discussed the details and findings of the trial in the following interview.

Why did you decide to explore the efficacy of a dexamethasone-free regimen?

Radhakrishnan: Dexamethasone is associated with both short-term and long-term side effects, especially when utilized across multiple cycles as an antiemetic. These adverse effects encompass hypertension, diabetes, peptic ulcers, insomnia, and an increased risk of infections. Surprisingly, there has been no examination of dexamethasone's role in the context of newer antiemetics.

Despite the addition of newer antiemetics such as NK1 antagonists, 5-HT3 antagonists, and olanzapine to the dexamethasone regimen, dexamethasone has not been replaced. This raises the question: why persist with a drug linked to significant toxicities? Is it feasible to maintain efficacy with newer antiemetics while omitting dexamethasone? Does dexamethasone truly have a role in the current era? These are the inquiries that motivated me to conduct the trial.

Was the study intended to compare dexamethasone with fosaprepitant?

Radhakrishnan: The study was not intended to compare dexamethasone with fosaprepitant. Rather, it aimed to compare a three-drug regimen free of dexamethasone (olanzapine, palonosetron, and fosaprepitant -- OPF) with the National Comprehensive Cancer Network-recommended three-drug OPD regimen (olanzapine, palonosetron, and dexamethasone). The OPD regimen is commonly utilized in resource-limited settings due to its affordability.

Why were the majority of trial participants patients with breast cancer?

Radhakrishnan: The study focused on patients undergoing single-day highly emetogenic chemotherapy. At our center, individuals with breast cancer receiving doxorubicin and cyclophosphamide form the largest subset within this group. Additionally, 25% of patients in the study received cisplatin for head and neck cancers. The study excluded patients who received dexamethasone as a premedication to prevent allergic reactions (e.g., paclitaxel and carboplatin for ovarian cancer) and those who received steroids as part of their chemotherapy regimen (e.g., R-CHOP -- rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone -- for lymphoma).

The chief outcomes were response rates for nausea and vomiting. What did you find?

Radhakrishnan: We discovered that patients receiving the three-drug dexamethasone-free OPF regimen exhibited superior control of vomiting and nausea throughout the overall period (up to 120 hours from the start of chemotherapy) compared with those on the dexamethasone-containing OPD regimen. Specifically, 79.6% of patients in the dexamethasone-free OPF arm did not experience vomiting during the overall period, as opposed to 48.8% in the OPD arm.

What did you find in terms of fatigue, drowsiness, and insomnia with the two regimens?

Radhakrishnan: Fatigue and drowsiness were more prevalent in the OPF arm during the acute period (first 24 hours after chemotherapy), while insomnia was observed more frequently in the OPD arm throughout the overall period (up to 120 hours after chemotherapy). Dexamethasone is known to enhance energy and alertness, leading us to believe that patients who did not receive a single dose of dexamethasone experienced more fatigue and drowsiness within the first 24 hours after chemotherapy compared with those who did. However, the administration of a single dose of dexamethasone was associated with insomnia persisting for up to 5 days after its administration.

Is there anything else you want to make sure oncologists understand about your study?

Radhakrishnan: Our study offers reassuring evidence that a three-drug dexamethasone-free regimen provides nausea and vomiting control rates that are comparable to those reported with dexamethasone-containing regimens.

Read the study here and expert commentary about it here.