Experts tackle 10 key questions and share their recommendations on how to address them.
Chemotherapy and radiotherapy induced nausea and vomiting remain major obstacles to patient comfort and treatment adherence, even after the 2023 MASCC/ESMO guideline update.
International oncology experts are now calling for clinicians to look beyond the recommendations and address unresolved issues that threaten to undermine progress in supportive care.
The updated guidelines, developed by 34 multidisciplinary health professionals and three patient advocates, reaffirmed the value of prophylaxis based on emetogenic risk: a four-drug regimen of 5-HT3 receptor antagonist (5-HT3-RA), NK1 receptor antagonist, dexamethasone, and olanzapine for highly emetogenic chemotherapy (HEC), and dual therapy with 5-HT3-RA and dexamethasone for moderately emetogenic chemotherapy (MEC). For higher-risk MEC, including carboplatin AUC ≥5 and certain antibody-drug conjugates (ADCs), the addition of NK1-RA was recommended.
In a review published in the European Journal of Cancer, researchers acknowledged that anti-emetic strategies could control CINV, but unaddressed issues remain.
“Through identifying the current gaps in the updated MASCC/ESMO guidelines and discussing the available evidence, we aim to address these issues and support oncologists who may encounter them in clinical practice,” they wrote.
“These and other questions need to be considered to help ensure choice of anti-emetic treatments provide optimal effectiveness in clinical practice.”
Individual risk factors further complicated clinical decisions, the authors wrote.
Younger age, female sex, prior CINV, or a history of motion sickness could turn an otherwise moderate-risk treatment into a high-risk scenario, yet such patient-level risks remain underrepresented in guideline frameworks.
“In clinical practice, choice of antiemetic prophylaxis may also be influenced by individual patient risk factors that can elevate the risk of CINV, meaning an otherwise MEC treatment regimen can pose a high risk to the individual patient,” the authors wrote.
“These factors may include younger age, female gender, anxiety, CINV in a previous episode, and a history of motion sickness or nausea and vomiting during pregnancy.
“Multidisciplinary teams may not always take these patient factors into account when making treatment decisions and they continue to not be fully addressed in the MASCC/ESMO guidelines. This may be largely due to difficulties in defining individual risk factors and the lack of adequate evidence.”
They said implementation also lagged behind evidence. Physicians often underestimated nausea, under-reporting by patients was common, and cost or complexity restricted access to anti-emetics.
These barriers could reduce adherence to both anti-emetic and cancer treatment, lowering dose intensity and, in some cases, forcing discontinuation.
Recognising these gaps, a group of oncology and supportive care specialists convened throughout 2024 to review the guideline update and highlight areas where evidence and practice diverge.
Questions and recommendations and comments included:
- Can a dexamethasone-sparing regimen be used with cisplatin (and other non-anthracycline and cyclophosphamide) based HEC chemotherapy? Single-dose dexamethasone may provide similar antiemetic control as multiple-day dexamethasone when combined with palonosetron and an NK-RA for cisplatin-based chemotherapy.
- Are lower doses (<10 mg) of olanzapine effective? There is evidence that olanzapine 5 mg/day, and possibly 2.5 mg/day or is as effective as standard-dose 10 mg/day in combination with triple antiemetic therapy.
- What individual risk factors mean MEC becomes HEC? A range of factors have been identified, including age, female sex, anxiety, a history of motion sickness or nausea during pregnancy, prior treatments, inadequate sleep before chemotherapy, and duration of CINV. Increased use of emesis risk calculators to estimate individual risk may be helpful.
- How should CINV in patients treated with new ADCs be managed? ADCs may be associated with a novel pattern of CINV, with onset of nausea at around two-three days and vomiting at around 10 days and the risk remaining high throughout each cycle. A two-drug regimen may possibly be sufficient for some patients, although triple therapy of 5-HT-RA, a NK-RA, and dexamethasone will be needed in others and may be considered the gold-standard approach. Anti-emetics with longer half-life and/or longer protection may be an appropriate option.
Related
- What is the emetogenic risk of FOLFOX/FOLFIRI/FOLFIRINOX regimens? Incidence of CINV for irinotecan-containing regimens is poorly recognised; triple therapy of dexamethasone, 5-HT3-RA and NK1-RA may be advisable as prophylaxis although evidence is limited. FOLFIRINOX regimen may have be more emetic than FOLFOX/FOLFIRI.
- When should a second agent be added to patients receiving LEC? If CINV control is inadequate with initial monotherapy, switching to an alternative agent should be considered. In patients with poor control of CINV in the previous cycle, the prophylaxis regimen recommended for the MEC could be considered. However, overtreatment may be a concern, and the addition of a second agent might only be considered if it addresses a particular issue.
- How should CINV be managed in patients receiving oral therapies? Data on the emetic risk potential of oral anticancer agents are very limited and guidance is based on the use of on-demand antiemetics, typically, a combination of 5-HT3-RA (days 1–7) and dexamethasone (days 1–3) should be considered. An NK1-RA may need to be added if this is inadequate and multiple dosing should also be considered.
- What is the best drug for breakthrough CINV? Deliver the optimal adapted prophylaxis from the first cycle and to assess the correct adherence to the treatment. Olanzapine if not used for primary prophylaxis. Cannabinoids may also be considered although evidence for their use and access is limited.
- What are the options for patients with CINV after following best guidance (i.e., already receiving four-drug regimen including olanzapine)? If CINV occurred in previous cycles, ensure guideline-recommended treatment was prescribed and received, with the correct dosing and duration. Check that nausea and vomiting is chemotherapy-induced, or whether other factors may be involved. Consider choice of 5-HT3-RA based on PK/PD characteristics (e.g. half-life, CYP2D6 metabolism). Consider increasing dexamethasone dose and/or duration. Also, if the patient received olanzapine 5 mg, increasing the dose to 10 mg may be needed.
- How should long delayed CINV be managed? The entire CINV risk period and not just the initial 24hr or even 120hr should be considered when choosing anti-emetic prophylaxis. Properties of anti-emetics, such as half-life and duration of effect, may be relevant. Addition of an NK1-RA to 5-HT3-RA and dexamethasone may reduce CINV over a seven-day period versus 5-HT3-RA plus dexamethasone.
The authors concluded that clinicians needed to be proactive, tailoring anti-emetic strategies to patient characteristics, drug-specific risks, and the realities of clinical practice, rather than relying solely on guideline categories.
CINV may be common, but its impact on quality of life and treatment outcomes is profound. Experts argue that closing the gaps through real-world evidence, formal studies of modified regimens, and a sharper focus on patient-specific risk would be critical to ensuring anti-emetic strategies keep pace with modern oncology.
“CINV is a frequent side effect of many chemotherapy regimens that impacts patients’ quality of life and can potentially reduce the effectiveness of treatment,” they wrote.
“Guideline-recommended prophylactic anti-emetic strategies can control CINV in many patients, but unaddressed issues remain.
“Through identifying the current gaps in the updated MASCC/ESMO guidelines and discussing the available evidence, we have addressed some of these issues and provide expert support to oncologists who may encounter them in clinical practice.
“These and other questions need to be considered in formal studies of anti-emetic prophylaxis, where possible, that will provide optimal effectiveness in clinical practice.”
