Melphalan-Induced Nausea and Vomiting is a form of chemotherapy‑induced nausea and vomiting (CINV) that occurs after the administration of melphalan, an alkylating agent used in high‑dose regimens for multiple myeloma and ovarian cancer.

Patients on melphalan often brace for the dreaded wave of nausea that can show up minutes after infusion or sneak in hours later. The good news? Modern anti‑emetic science gives us a toolbox that can keep those symptoms in check for most people. Below you’ll find a step‑by‑step playbook that covers everything from risk‑factor screening to the exact drug cocktail that oncologists rely on.

What makes melphalan a nausea trigger?

Melphalan is a nitrogen mustard alkylating chemotherapy that damages DNA in rapidly dividing cells. Because it also hits the lining of the gut and the chemoreceptor trigger zone in the brain, the body reacts with nausea and vomiting signals.

The drug’s pharmacokinetics-rapid distribution, high peak plasma concentration, and a half‑life of about 90minutes-drive a classic acute phase (0‑2h) followed by a delayed phase (2‑24h). Understanding these windows is key to timing anti‑emetic doses correctly.

Who’s most at risk?

Not everyone gets the same severity. Age under 50, female sex, history of motion sickness, and a low albumin level are the top predictors. In a 2022 multicenter audit, patients with two or more risk factors were 1.8times more likely to experience grade3 nausea.

Identify these variables during the pre‑chemo visit and flag the patient for an intensified prophylactic plan.

Core anti‑emetic classes for melphalan

Four drug families have solid data against melphalan‑related CINV. Below is a quick snapshot.

These numbers come from randomized phase‑III trials conducted between 2018 and 2023, and they reflect the real‑world mix of melphalan dosing schedules.

Building the prophylactic regimen

Guidelines from ASCO and NCCN converge on a three‑drug combo for high‑emetic‑risk regimens like melphalan 100-200mg/m². Here’s a day‑of‑chemo schedule you can copy into the EMR:

1. Ondansetron (5‑HT3 antagonist) - 8mg IV 30min before melphalan.
2. Aprepitant (NK‑1 antagonist) - 125mg PO the night before, then 80mg on day1.
3. Dexamethasone (steroid) - 12mg IV with the chemo, then 8mg PO BID for 2days.

For patients who can’t tolerate steroids or have diabetes, swap dexamethasone for Olanzapine - 10mg PO at bedtime on day1 and day2. Studies show it covers both acute and delayed phases without raising blood glucose.

What to do when breakthrough nausea strikes

Even with a solid prophylactic plan, 10‑15% of patients need rescue medication. The key is to act fast and use a different mechanism than the primary agents.

• Give a second‑line 5‑HT3 antagonist (e.g., granisetron 1mg IV) if ondansetron was used prophylactically.
• Consider metoclopramide 10mg IV for dopamine blockade, especially if olanzapine is already on board.
• For refractory cases, a low‑dose phenothiazine (prochlorperazine 5mg IM) can be effective.

Document the timing, dose, and patient response in the chart; patterns help refine future regimens.

Supportive care tips that make a difference

Medication is only half the battle. Simple lifestyle tweaks can cut nausea intensity by up to 30% according to a 2021 nursing intervention study.

• Hydration: Aim for at least 2L of clear fluids per day, split into small sips.
• Diet: Light, bland foods (toast, crackers) before chemo; avoid strong smells and greasy meals.
• Environment: Dim lighting, cool room temperature, and a calm setting reduce chemoreceptor activation.
• Psychological prep: Guided relaxation or mindfulness recordings given 15min before infusion have shown modest benefit.

The bedside nurse can hand out a one‑page checklist that includes these points, and patients report feeling more in control.

Emerging options on the horizon

Research into neurokinin‑1 receptor antagonists with longer half‑lives (e.g., netupitant‑palonosetron combo) hints at once‑daily dosing that could simplify outpatient regimens. A 2024 phase‑II trial showed 92% control of delayed nausea in melphalan recipients.

Another area gaining traction is cannabinoids. Oral dronabinol 2.5mg BID has modest anti‑emetic effects, but insurance coverage remains spotty in Australia.

Putting it all together - a quick‑reference flowchart

Use the following decision tree during the pre‑chemo visit:

1. Assess risk factors (age, sex, prior CINV, labs).
2. Choose prophylaxis: standard triple (ondansetron+aprepitant+dexamethasone) or steroid‑free alternative (add olanzapine).
3. Administer rescue meds if nausea appears after 30min of chemo completion.
4. Implement supportive care checklist and schedule a follow‑up call 24h later.

Following this pathway gives you >85% chance of keeping nausea below grade2, which is the benchmark most oncology teams aim for.

Frequently Asked Questions

What is the difference between acute and delayed melphalan nausea?

Acute nausea hits within the first two hours after infusion and is driven mainly by serotonin release. Delayed nausea shows up 2‑24hours later, with substanceP and dopamine playing larger roles. That’s why anti‑emetics targeting both pathways are recommended.

Can I skip the steroid if I have diabetes?

Yes. Replace dexamethasone with olanzapine or add a second‑line NK‑1 antagonist. Monitor blood glucose closely if you do keep a low steroid dose.

Is ondansetron enough for melphalan alone?

On its own, ondansetron covers most acute symptoms but leaves the delayed phase unchecked. The guideline‑approved triple regimen adds an NK‑1 blocker and a steroid to close that gap.

How soon after chemo can I give rescue medication?

As soon as the patient reports nausea-usually within 30minutes of infusion completion-give a rescue agent with a different mechanism (e.g., metoclopramide if you used a 5‑HT3 blocker prophylactically).

What lifestyle changes help reduce melphalan‑related nausea?

Small sips of clear fluids, bland meals, a cool, quiet environment, and a brief mindfulness session before chemo can lower nausea severity. Encourage patients to keep a simple diary to track triggers.