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Sickness from chemotherapy is now largely preventable. The anti-sickness medicines you are given depend on how likely your chemotherapy is to cause sickness: for the strongest regimens that is four medicines before treatment and some for the days after, for the mildest none at all. If you are still sick, tell your team: there is a next step.
Prophylaxis is chosen by the emetic risk of the regimen, defined as the chance of vomiting in the first 24 hours without prophylaxis (high, above 90 per cent; moderate; low; minimal), adjusted for patient factors such as female sex and younger age. MASCC/ESMO (2023) recommend for high emetic risk a four-drug regimen before chemotherapy: a 5-HT3 receptor antagonist, dexamethasone, an NK1 receptor antagonist (aprepitant, fosaprepitant, netupitant or fosnetupitant with palonosetron, or rolapitant) and olanzapine (I, A). For delayed nausea after cisplatin and other non-anthracycline-cyclophosphamide regimens, dexamethasone and olanzapine continue on days 2 to 4 (II, B); after anthracycline with cyclophosphamide, dexamethasone stops after day 1 and olanzapine alone continues on days 2 to 4 (II, B). Olanzapine 10 mg is the best investigated dose; 5 mg or a bedtime dose is an option where sedation matters (II, B).
For moderate emetic risk, MASCC/ESMO add an NK1 receptor antagonist for carboplatin at AUC 5 or more and for women under 50 having oxaliplatin, use a 5-HT3 receptor antagonist with a steroid for other regimens, and limit the steroid to day 1. Low emetic risk gets a single agent before treatment and nothing for the delayed phase; minimal risk gets none. ASCO (2020) keeps dexamethasone when checkpoint inhibitors are given with chemotherapy and gives no routine prophylaxis for checkpoint inhibitors alone. For breakthrough nausea and vomiting the evidence favours olanzapine 10 mg once daily for 3 days (II, B); for high-dose chemotherapy before stem cell transplant, a 5-HT3 receptor antagonist with dexamethasone and aprepitant (I, A), with olanzapine to be considered.
Why: The emetic risk of the most sickness-causing drug in the regimen decides which anti-sickness medicines are needed.
“High emetic risk is defined as a risk of more than 90% of vomiting.”
Why: Two people on the same regimen do not have the same risk; women and younger people are sick more often.
“patient demographics such as sex (women are at a higher risk than men) and age (younger patients have a higher risk than older)”
Why: Large trials showed that adding olanzapine to the older three-drug combination prevents more nausea, so it is now part of the standard set.
“Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC.”
Why: Sickness after cisplatin often peaks a few days later; the evidence for stopping the steroid after day 1 in these regimens is not yet conclusive.
“DEX and olanzapine on days 2 to 4 is suggested to prevent delayed nausea and vomiting”
Why: Trials showed the extra days of steroid add nothing after this regimen, so they can be spared.
“There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC.”
Why: 10 mg is the dose most studied; 5 mg works better than nothing but has not been shown equal to 10 mg.
“If sedation is a concern, a starting daily dose of 5 mg and/or administration at bedtime is an option”
Why: These two groups are sick more often than others on moderate-risk treatment, and the third drug helps them.
“for patients undergoing carboplatin (AUC ≥ 5) and women < 50 years of age receiving oxaliplatin-based treatment”
Why: Trials found a single day of steroid as good as several days for these regimens, with fewer steroid side effects.
“it is recommended that the administration of steroids should be limited to day 1 in moderately emetogenic chemotherapy regimens”
Why: Most people on these treatments are not sick, so routine medicines would add side effects without benefit.
“No antiemetic prophylaxis is recommended for minimal emetic potential therapy, and single agents recommended for low emetic potential chemotherapy for acute emesis, but no prophylaxis is recommended for delayed emesis.”
Why: There is no evidence that the steroid weakens immunotherapy in these combinations, and the immunotherapy drugs on their own rarely cause sickness.
“There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy.”
Why: High-dose conditioning causes sickness over several days; this combination is the best supported.
“Olanzapine could be considered part of the antiemetic regimen.”
Why: Each day of cisplatin brings its own sickness, and the delayed phase follows the last dose.
“Olanzapine (in a dose of 5 mg at bedtime), aprepitant, and dexamethasone should be given once daily on the days of chemotherapy and until 2 days post-chemotherapy”
Why: Olanzapine has the best evidence for rescue; rescue medicines are usually those used for the next higher level of risk.
“The available evidence for breakthrough nausea and vomiting suggests the use of 10-mg olanzapine, once daily for 3 days”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
The MASCC/ESMO 2023 update is the most recent international guideline and the only one read here in full. It makes olanzapine a fixed part of a four-drug regimen for all high emetic risk chemotherapy (I, A), which it notes is in line with ASCO, keeps dexamethasone on days 2 to 4 after cisplatin and other non-anthracycline-cyclophosphamide regimens, and drops it after day 1 for anthracycline with cyclophosphamide. ASCO's latest update (2020) was read only as an abstract: it left its adult recommendations unchanged apart from adding olanzapine as an option in stem cell transplant and a 5 mg olanzapine dose, and it is the source for keeping dexamethasone with chemotherapy plus checkpoint inhibitors. Where the two differ is the dose of olanzapine: ASCO offers 5 mg as an option, while MASCC/ESMO say 10 mg is the best investigated and that 5 mg has not been shown to be as effective. NCCN (2023) and Cancer Care Ontario (2019) were not read; a 2024 comparison of all four says they share many fundamental similarities and that evidence is thin for low and minimal risk regimens.
MASCC and ESMO, Supportive Care in Cancer 2023 · MASCC and ESMO, Supportive Care in Cancer 2023 · MASCC and ESMO, Supportive Care in Cancer 2023 · MASCC and ESMO, Supportive Care in Cancer 2023 · ASCO, Journal of Clinical Oncology 2020 · Supportive Care in Cancer 2024
Where it differs: ASCO's 2020 update added a 5 mg olanzapine dose for adults as an option alongside 10 mg.
Evidence: MASCC/ESMO (2023) found that 5 mg is better than placebo but that no adequately powered study has compared it with 10 mg, so they keep 10 mg as the best investigated dose and 5 mg as an option where sedation is a concern (II, B).
ASCO, Journal of Clinical Oncology 2020 · MASCC and ESMO, Supportive Care in Cancer 2023
Where it differs: Stops dexamethasone after day 1 for cisplatin as well as for anthracycline with cyclophosphamide, to spare steroid side effects such as poor sleep, high blood sugar and indigestion.
Evidence: MASCC/ESMO judged the trials inconclusive for cisplatin and kept the 3 to 4 day regimen; they note that a few studies have tested a 1-day regimen in cisplatin, one showing comparable efficacy, and that none of the trials it considered included olanzapine. The 2025 review by members of the committee lists this as an open question.
MASCC and ESMO, Supportive Care in Cancer 2023 · European Journal of Cancer 2025
Where it differs: Adds acupuncture or electroacupuncture, food-based approaches, or progressive muscle relaxation with or without guided imagery to the drug regimen.
Evidence: MASCC/ESMO (2023) could make recommendations for these three, found major methodological flaws in many trials, could make no recommendation for ginger because the evidence conflicts, and none for aromatherapy, hypnosis in adults, music therapy or reflexology.
A cheap, old antipsychotic at a low dose is one of the best anti-sickness drugs for chemotherapy. Make sure every cancer unit in the world uses it.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Four-drug regimen with olanzapine before high emetic risk chemotherapy, both cisplatin-type and anthracycline with cyclophosphamide “Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC.” | I, A | MASCC and ESMO, Supportive Care in Cancer 2023 |
| Dexamethasone and olanzapine on days 2 to 4 after non-anthracycline-cyclophosphamide high emetic risk chemotherapy “DEX and olanzapine on days 2 to 4 is suggested to prevent delayed nausea and vomiting” | II, B | MASCC and ESMO, Supportive Care in Cancer 2023 |
| Olanzapine alone on days 2 to 4 after anthracycline with cyclophosphamide | II, B | MASCC and ESMO, Supportive Care in Cancer 2023 |
| Olanzapine 10 mg, with 5 mg or a bedtime dose as an option where sedation is a concern “The best investigated dose is 10 mg.” | II, B | MASCC and ESMO, Supportive Care in Cancer 2023 |
| Four drugs for multiple-day cisplatin | I/A (acute); II/B for the number of days | MASCC and ESMO, Supportive Care in Cancer 2023 |
| 5-HT3 receptor antagonist, dexamethasone and aprepitant for high-dose chemotherapy before stem cell transplant | I/A | MASCC and ESMO, Supportive Care in Cancer 2023 |
| Olanzapine for breakthrough nausea and vomiting | II/B | MASCC and ESMO, Supportive Care in Cancer 2023 |
Shares Low-dose olanzapine and generic antiemetic bundles in every guideline and formulary, Granisetron, Palonosetron, Aprepitant (and fosaprepitant) and the tags protocol, nausea-and-vomiting.
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