Study Finds Poor Adherence to Guidelines in Preventing Chemotherapy-Induced Nausea and Vomiting

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Adherence to antiemetic guidelines for the prevention of chemotherapy-induced nausea and vomiting has been shown to improve patient outcomes. However, a new study suggests that physicians are still struggling to reach attainable adherence targets in antiemetic prophylaxis.1

According to data presented at the 2018 Palliative and Supportive Care in Oncology Symposium, less than half of physicians achieved greater than 90% adherence to established, evidence-based, antiemetic guidelines for highly emetogenic chemotherapy.1 The retrospective analysis of more than 10,000 highly emetogenic chemotherapy courses of therapy initiated between 2012 and 2017 found that 32% of individual physicians had greater than 90% adherence to antiemetic guidelines for cisplatin. Compliance with antiemetic guidelines for anthracycline plus cyclophosphamide was higher, with 56% of physicians having greater than 90% adherence.

Eric J. Roeland, MD, FAAHPM

Eric J. Roeland, MD, FAAHPM

“Cisplatin was defined as highly emetogenic chemotherapy back in the 1990s, whereas anthracyclines and cyclophosphamide were defined as highly emetogenic in 2003. And this data suggests that we are still struggling with adherence to antiemetic guidelines,” said Eric J. Roeland, MD, FAAHPM, a medical oncologist at Massachusetts General Hospital, Boston. “These results make me extremely concerned about prophylaxis for patients who receive carboplatin, which was just defined as highly emetogenic chemotherapy in the updates of 2016 to 2018. Based on these results, interventions are needed to bolster triple antiemetic prophylaxis in highly emetogenic chemotherapy.”

As Dr. Roeland explained, U.S. National Antiemetic Guidelines recommend upfront triple prophylaxis for patients receiving highly emetogenic chemotherapy, which is defined as chemotherapy with a high incidence (90% or greater) of nausea and vomiting. Although existing data have shown gaps in guideline compliance, said Dr. Roeland, variation between individual physicians is less studied, and a realistic target compliance rate remains unknown.

Antiemetic Prophylaxis

  • Less than half of physicians had greater than 90% adherence to established, evidence-based, antiemetic guidelines for highly emetogenic chemotherapy.
  • For cisplatin, just 32% of individual physicians had greater than 90% adherence to antiemetic guidelines.

For this study, Dr. Roeland and colleagues used the IBM Explorys database, which includes more than 5 million patients and 350,000 clinicians, to identify highly emetogenic chemotherapy courses of therapy initiated between 2012 and 2017. Guideline adherence was defined as receipt of triple antiemetic prophylaxis (neurokinin 1 [NK1] receptor antagonist plus 5-hydroxytryptamine receptor antagonist plus dexamethasone) at chemotherapy initiation.

“It’s been shown that patients who experience nausea and vomiting after their first cycle of chemotherapy are four to five times more likely to experience nausea and vomiting in subsequent cycles. This really highlights the importance of upfront prophylaxis,” said Dr. Roeland.

Patient courses for at least 7-day cycles of cisplatin or anthracycline plus cyclophosphamide or carboplatin (at least 14-day cycles as a proxy for AUC ≥ 4) were ascribed to oncologists and/or hematologists based on encounter frequency. Dr. Roeland and colleagues then ranked physicians treating patients with at least five highly emetogenic chemotherapy courses and evaluated guideline compliance and individual physician variation.

Poor Adherence to Antiemetic Guidelines

As Dr. Roeland reported, 10,074 highly emetogenic chemotherapy courses were identified and attributed to 451 unique physicians. Results showed that overall antiemetic guideline compliance with cisplatin and anthracycline plus cyclophosphamide averaged 68% and 81%, respectively. When ranked by compliance, the top 20% of physicians were up to 2.5 times as compliant as the bottom 20%, the authors noted.

“Cisplatin is the poster child for nausea and vomiting, and just 32% of physicians had greater than 90% compliance to the guidelines,” said Dr. Roeland, who noted that adherence rates for the remaining 68% were evenly distributed from 0% to 90%.

Adherence was higher for anthracycline plus cyclophosphamide, but just 56% of physicians had greater than 90% compliance to the guidelines, Dr. Roeland reported. For carboplatin, 62% of physicians had up to 10% compliance, and another 17% of physicians had between 11% and 20% compliance. However, the authors noted that the majority of these data preceded guideline inclusion of carboplatin as highly emetogenic chemotherapy at a dose of AUC ≥ 4. Dr. Roeland also reported that the lack of institution-specific data in the database was a major limitation of the study.

“Is adherence a result of the physicians themselves or the automatic order sets included for oncologists at institutions now reliant on their electronic medical records to simply click to order antiemetics?” Dr. Roeland observed. “We cannot, of course, determine causality based on this study design.”

According to the authors, hundreds of physicians had greater than 90% compliance with guidelines, suggesting 90% is a realistic target. However, the majority exhibited substantial gaps in use of NK1 receptor antagonists in highly emetogenic chemotherapy, placing patients unnecessarily at risk for chemotherapy-induced nausea and vomiting.

“This study shows considerable physician-level variation in triple antiemetic prophylaxis guideline adherence for highly emetogenic chemotherapy,” said Dr. Roeland. “The key now is to understand the barriers to adherence, so we can start to improve it.”

Audience Questions

Chair of the session, Esme Finlay, MD, a medical oncologist at the University of New Mexico School of Medicine, asked about the dosing of cisplatin used in the definition of highly emetogenic chemotherapy.

“We defined a certain interval between infusions to ensure we were not including the weekly low dose for patients who are also getting radiation,” said Dr. Roeland. “The challenge in finding those doses was more related to using the time in between intervals as a surrogate marker of the dose itself. In this analysis, we were looking at higher doses of cisplatin, not the lower doses.”

Another member of the audience asked whether patients in the study had gastrostomy tubes for feeding and whether that might impact choices made by physicians regarding antiemetics.

“We weren’t able to look at that specifically,” said Dr. Roeland. “However, even if patients have a gastronomy tube in place, although vomiting might not be as big of a concern, nausea still is. Even grade 1 nausea over a long period is more impactful on quality of life than severe nausea and vomiting for 1 or 2 days.” 

DISCLOSURE: Dr. Roeland has relationships with AIM Specialty Health, Helsinn Healthcare, Napo Pharmaceuticals, Oragenics, ProNova, Pfizer, Depomed, and Eisai. The study was sponsored by Helsinn Therapeutics.


1. Roeland E, Ruddy KJ, LeBlanc TW, et al: What the HEC? Physician variation and attainable compliance targets in antiemetic prophylaxis. 2018 Palliative and Supportive Care in Oncology Symposium. Abstract 74. Presented November 16, 2018.