ASCO Reading Room | Venkatraman Radhakrishnan on dexamethasone for antiemetic prophylaxis

With the advent of new antiemetic agents, is dexamethasone still a necessary part of antiemetic prophylaxis for patients with breast cancer or other cancers receiving highly emetogenic chemotherapy (HEC)?

Venkatraman Radhakrishnan, MD, of the Adyar Cancer Institute in Chennai, India, and colleagues explored this question in a randomized clinical trial (RCT). “To our knowledge, no RCTs have been published on prophylactic regimens for chemotherapy-induced nausea and vomiting for HEC without dexamethasone,” the researchers noted in JCO Global Oncology.

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

“To our knowledge, in our manuscript we present the results of the first blinded phase III RCT demonstrating the efficacy of a prophylactic antiemetic regimen without DEX in the era of newer antiemetics, such as NK-receptor antagonists. 1, 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 effectiveness of a dexamethasone-free diet?

Radhakrishnan: Dexamethasone is associated with short- and long-term side effects, particularly when used over multiple cycles as an antiemetic. These side effects include hypertension, diabetes, peptic ulcers, insomnia, and increased risk of infections. Surprisingly, the role of dexamethasone in the context of newer antiemetics has not been examined.

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 possible to maintain the effectiveness of newer antiemetics while omitting dexamethasone? Does dexamethasone really have a role to play in today’s times? It was these investigations that motivated me to lead the trial.

Was the study intended to compare dexamethasone to fosaprepitant?

Radhakrishnan: The study did not aim to compare dexamethasone to fosaprepitant. Rather, it aimed to compare a three-drug regimen without dexamethasone (olanzapine, palonosetron, and fosaprepitant – OPF) with the three-drug OPD regimen recommended by the National Comprehensive Cancer Network (olanzapine, palonosetron, and dexamethasone). The OPD regimen is commonly used in resource-limited settings due to its affordability.

Why did the majority of trial participants have breast cancer?

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

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

Radhakrishnan: We found that patients receiving the three-drug OPF regimen without dexamethasone had superior control of vomiting and nausea throughout the overall period (up to 120 hours after the start of chemotherapy) compared to those receiving the OPD diet containing dexamethasone. Specifically, 79.6% of patients in the OPF arm without dexamethasone did not experience vomiting during the entire period, compared to 48.8% in the OPD arm.

What did you notice in terms of fatigue, sleepiness and insomnia with both diets?

Radhakrishnan: Fatigue and somnolence were more common in the OPF arm during the acute period (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 improve energy and alertness, leading us to believe that patients who did not receive a single dose of dexamethasone experienced more fatigue and drowsiness in the 24 hours after chemotherapy than those who who received it. However, administration of a single dose of dexamethasone was associated with insomnia persisting for up to 5 days after 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 regimen without dexamethasone provides rates of nausea and vomiting control comparable to those reported with dexamethasone-containing regimens.

Read the study here and expert commentary on it here.