OncologyTier 1Approach to a presentation

Side effects of systemic cancer therapy - vomiting

Red flags

Faeculent vomiting, colicky pain, distension, absent bowel sounds -> bowel obstruction
Projectile or early-morning vomiting with headache, papilloedema -> raised ICP
Haematemesis or coffee-ground vomit -> upper GI bleed (mucositis, ulcer, varices, thrombocytopenia)
Fever with neutropenia -> neutropenic sepsis - treat this first
Severe dehydration, oliguria, postural drop, rising creatinine -> admit for IV fluids
Hypokalaemia + metabolic alkalosis + tetany -> severe protracted vomiting
Hypotension, hyponatraemia, hyperkalaemia -> adrenal insufficiency
Inability to keep down oral chemotherapy, anticonvulsants, opioids, immunosuppressants or antimicrobials -> the vomiting is now a treatment failure risk, not just a symptom
Confusion + polyuria -> hypercalcaemia

Chemotherapy-induced emesis - by phase

Phase	Timing	Mediator	Best-covered by
Acute	0-24 h	Serotonin (5-HT3) from enterochromaffin cells	5-HT3 antagonist + dexamethasone
Delayed	24-120 h	Substance P (NK1) centrally	NK1 antagonist + dexamethasone
Anticipatory	before the dose	Conditioned/cortical	Benzodiazepine
Breakthrough	despite prophylaxis	Mixed	Add a different class
Refractory	recurrent across cycles	Mixed	Escalate the whole regimen

Non-chemotherapy causes to exclude

Mechanical - malignant bowel obstruction, gastric outlet obstruction, gastroparesis, severe constipation/impaction
Metabolic - hypercalcaemia, hyponatraemia, uraemia, hepatic failure, DKA, adrenal insufficiency
CNS - brain metastases, leptomeningeal disease, raised ICP, vestibular disease
Drugs - opioids, antibiotics, NSAIDs, digoxin, antifungals, oral targeted agents
GI mucosal - mucositis, oesophagitis (candida, HSV), gastritis, peptic ulcer, radiation enteritis
Infection - gastroenteritis, C. difficile, sepsis, neutropenic enterocolitis (typhlitis)
Radiotherapy to abdomen or brain

Emetogenic potential of the regimen given - look it up rather than assuming
Timing - before treatment, within 24 h, or days 2-5
Number of episodes, volume, content (undigested food, bile, faeculent, blood)
What prophylaxis was prescribed and whether the take-home doses were actually taken
Response at previous cycles
Bowel habit, last bowel motion, flatus
Oral intake, fluid intake, weight change, urine output
Headache, visual change, neurological symptoms
Opioid and other drug changes
Risk factors for poor control: female, age <50, history of motion sickness or hyperemesis in pregnancy, anxiety, low prior alcohol intake, poor control at a previous cycle

Volume status - postural BP, HR, mucous membranes, JVP, capillary refill; weigh the patient
Sepsis screen and temperature
Abdomen - distension, tenderness, succussion splash, bowel sounds (tinkling/absent), organomegaly, ascites, hernial orifices
PR - impaction, empty rectum with obstruction
Mouth - mucositis, candidiasis
Neurology - fundoscopy, cranial nerves, focal signs
Signs of chronic vomiting: dental erosion, parotid swelling, Mallory-Weiss tear

UEC, corrected calcium, magnesium, LFT, glucose, FBE, CRP, venous gas
- Look for hypokalaemic hypochloraemic metabolic alkalosis in protracted vomiting
Blood cultures if febrile
Erect CXR + abdominal x-ray if obstruction or perforation suspected
CT abdomen/pelvis - defines level and cause of obstruction, and whether it is single or multi-level (this determines whether surgery is even an option)
CT/MRI brain if neurological features or unexplained persistent vomiting
Morning cortisol, TSH if endocrine cause possible
C. difficile toxin and stool culture if diarrhoea coexists

A. Prophylaxis by emetogenic risk - the core of the topic

Prescribe before the first dose. Rescuing a patient who has already vomited is far harder than preventing it.

Risk	Examples	Prophylaxis
High (>90%)	Cisplatin, carmustine, dacarbazine, streptozocin, high-dose busulfan, procarbazine, cyclophosphamide >1500 mg/m2, AC in breast cancer	NK1 antagonist + 5-HT3 antagonist + dexamethasone (+/- olanzapine = quadruplet)
Moderate (30-90%)	Carboplatin (treat as high-risk - add NK1), oxaliplatin, doxorubicin, irinotecan, ifosfamide	5-HT3 antagonist + dexamethasone (+ NK1 for carboplatin)
Low (10-30%)	Paclitaxel, docetaxel, etoposide, gemcitabine, 5-FU, pemetrexed	Dexamethasone or a 5-HT3 antagonist
Minimal (<10%)	Bleomycin, vinca alkaloids, most monoclonals, TKIs	None routinely

Dexamethasone must be continued into the delayed phase (days 2-4) for high-risk regimens
Antiemetic agents
- 5-HT3: ondansetron, granisetron; palonosetron has a long half-life and covers the delayed phase better
- NK1: aprepitant, fosaprepitant, netupitant (as NEPA with palonosetron), rolapitant
  - Aprepitant is a CYP3A4 inhibitor - interacts with dexamethasone (halve the dose), warfarin, and some chemotherapy
- Olanzapine 5-10 mg nocte days 1-4 - the biggest recent improvement, especially for nausea
- Dexamethasone; metoclopramide, haloperidol, prochlorperazine, lorazepam as adjuncts

B. Established/breakthrough vomiting

Add an agent from a different receptor class; give it regularly, not PRN
Change route - the patient cannot absorb oral antiemetics while vomiting: use IV or subcutaneous infusion
IV fluid and electrolyte replacement - potassium, magnesium
Escalate prophylaxis at the next cycle rather than repeating what failed
Consider dose reduction or regimen change if refractory

C. Cause-specific

Malignant bowel obstruction - NG decompression, IV fluids, hyoscine butylbromide (antisecretory), octreotide, dexamethasone, haloperidol; stop prokinetics; surgical/stenting/venting gastrostomy review
Raised ICP - dexamethasone 8-16 mg, urgent imaging, radiotherapy/neurosurgical referral
Constipation - aggressive laxatives; PR if impacted
Hypercalcaemia - fluids + bisphosphonate
Gastroparesis - metoclopramide, small meals

D. Anticipatory vomiting

Under-classifying the regimen: carboplatin behaves as highly emetogenic - it needs an NK1 antagonist
Stopping dexamethasone after day 1 for a high-risk regimen - the delayed phase is uncovered
Relying on a 5-HT3 antagonist for delayed emesis
Prescribing oral antiemetics to a patient who is actively vomiting
Prokinetics (metoclopramide) in complete mechanical obstruction
Forgetting the aprepitant-dexamethasone CYP3A4 interaction
QT prolongation with ondansetron plus other QT-prolonging drugs; check potassium and magnesium
Extrapyramidal reactions to metoclopramide and prochlorperazine, especially in young women - akathisia is often mislabelled as anxiety
Missing that the patient has been unable to take oral anticonvulsants, immunosuppressants or antimicrobials
Not documenting poor control so the next cycle repeats the same failed regimen

"How many times did you actually vomit, and on which days after treatment?"
"Bring in the box of anti-sickness tablets so we can see exactly what you've been taking."
"The tablets for days two to five work differently from the ones on the day - both matter."
"You should not have to just put up with this. If it happened this cycle, we change the plan for next cycle."
"Have you been able to keep your other medications down?"
To a patient dreading treatment: "Feeling sick at the thought of coming in is common and it's a learned reaction - there's a specific treatment for it."

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