CONCEPTUAL SUMMARY
EMETIC RISK CLASSIFICATION OF CHEMOTHERAPY:
- High emetic risk (HEC) — > 90% incidence without prophylaxis:
- cisplatin (prototype),
- AC combination (anthracycline + cyclophosphamide — classified as HEC regardless of individual agent risk),
- high-dose melphalan (HSCT conditioning),
- BEAM conditioning regimen.
- Moderate emetic risk (MEC) — 30–90%:
- oxaliplatin (FOLFOX), carboplatin, irinotecan, cyclophosphamide (non-AC), doxorubicin alone, temozolomide ≥ 75 mg/m²/day.
- Low emetic risk — 10–30%: paclitaxel, pemetrexed (single agent), docetaxel.
- Minimal emetic risk — < 10%: vinca alkaloids (vincristine, vinblastine, vinorelbine — all minimal risk), bleomycin, hormonal agents (letrozole, anastrozole), erlotinib, capecitabine.
TYPES OF CINV:
- Acute: occurs within 24 hours of chemotherapy; primary neurotransmitter = SEROTONIN.
- Delayed: occurs > 24 hours after chemotherapy, up to 5–7 days; primary neurotransmitter = SUBSTANCE P; cisplatin peaks at 48–72 hours and can last 6–7 days; triggered by cisplatin, carboplatin, cyclophosphamide, and anthracyclines.
- Anticipatory: conditioned reflex BEFORE chemotherapy triggered by sensory cues (sight, smell, sound of treatment environment); primary cause = POOR ANTIEMETIC CONTROL in previous cycles; treated with benzodiazepines (lorazepam).
- Breakthrough: nausea/vomiting that occurs DESPITE appropriate prophylaxis; treated by adding an agent from a DIFFERENT pharmacological class than the initial prophylactic regimen.
PATIENT-SPECIFIC RISK FACTORS FOR INCREASED CINV (HIGH-YIELD)
Female sex, age < 50 years (younger patients at higher risk — older patients at LOWER risk), minimal or no alcohol consumption (alcohol use history ≥ 5 drinks/week is PROTECTIVE — reduces CINV risk), history of motion sickness, history of morning sickness during pregnancy, history of poor CINV control with prior chemotherapy, high anxiety levels.
Risk factors for REDUCED CINV:
older age, male sex, regular/heavy alcohol use. Smoking history has NO significant impact on CINV risk.
ANTIEMETIC DRUG CLASSES AND MECHANISMS:
- 5-HT3 receptor antagonists (serotonin antagonists): ondansetron, granisetron, dolasetron, palonosetron.
- MOA: peripheral blockade of serotonin release from enterochromaffin cells in GI tract + central blockade in medulla (CTZ).
- Most effective for ACUTE CINV.
- Palonosetron is a SECOND-GENERATION 5-HT3 antagonist with unique allosteric and facilitative binding — longer half-life (40 hours) — superior efficacy for both acute AND delayed CINV when no NK1 antagonist is used.
- Palonosetron preferred for MEC without NK1 antagonist. NOT all 5-HT3 antagonists are equivalent (palonosetron superior). ORAL = INTRAVENOUS for 5-HT3 antagonists (equivalent efficacy due to high GI serotonin receptor density).
- 5-HT3 antagonists NOT recommended for delayed CINV prevention in HEC protocols.
- Common toxicities: headache, constipation (NOT diarrhea — diarrhea is NOT a typical 5-HT3 toxicity), QTc prolongation (NOT palonosetron). Hypertension is NOT a 5-HT3 side effect.
- NK1 receptor antagonists: aprepitant (PO), fosaprepitant (IV prodrug → aprepitant), rolapitant (PO), netupitant/palonosetron (NEPA), fosnetupitant/palonosetron (IV NEPA).
- MOA: block substance P from binding NK1 receptors centrally. Highly effective for delayed CINV. DRUG INTERACTIONS — CYP3A4: aprepitant, fosaprepitant, netupitant, fosnetupitant INHIBIT CYP3A4 → INCREASE dexamethasone levels → dexamethasone dose MUST be reduced to 12 mg (from 20 mg) when co-administered. Rolapitant EXCEPTION: does NOT inhibit CYP3A4, does NOT require dexamethasone dose reduction. Aprepitant INDUCES CYP2C9 → DECREASES warfarin levels → lower INR (subtherapeutic, NOT supratherapeutic) — this is clinically important (monitor INR at 7–10 days after aprepitant). Aprepitant also induces oral contraceptive metabolism — alternative contraception needed during and 1 month after. Rolapitant has a very long half-life (~7 days for oral, 76 days for IV) — superior delayed phase coverage with single dose. Fosaprepitant 150 mg IV day 1 provides complete NK1 coverage for entire cycle — no additional oral aprepitant needed on days 2–3. Aprepitant 125 mg PO day 1 requires 80 mg PO daily on days 2–3.
- Corticosteroids (dexamethasone): mechanism in CINV unknown — likely prostaglandin inhibition and CNS anti-inflammatory effects. Adding dexamethasone to a 5-HT3 antagonist provides approximately 20% ADDITIONAL antiemetic protection. Effective for both acute and delayed CINV. Used for treatment of breakthrough CINV. NOT for anticipatory CINV (benzodiazepines are used for anticipatory). Standard acute dose: 20 mg without NK1 antagonist; 12 mg with NK1 antagonist. Delayed phase dose: 8 mg daily days 2–4.
- Toxicities: hyperglycemia (most important — NOT low blood pressure, easy bruising, or weight loss), insomnia (NOT drowsiness), dyspepsia. Does NOT cause QTc prolongation or drowsiness.
- Olanzapine (atypical antipsychotic): MOA = blocks dopaminergic (D2), serotonergic (5-HT2, 5-HT3), histaminergic, and muscarinic receptors. Used in multi-drug HEC prophylaxis (4-drug regimen) and for breakthrough CINV. Now added as fourth drug for HEC regimens in high-risk patients.
- Toxicities: somnolence/sedation (most common), weight gain, constipation (NOT diarrhea), QTc prolongation. Correct dose: 5–10 mg daily days 1–4. NOT associated with diarrhea.
- Dopamine antagonists: metoclopramide, prochlorperazine, haloperidol, droperidol, promethazine. Risk of extrapyramidal symptoms (EPS) — muscular spasms, oculogyric crisis, pill-rolling, motor restlessness. Treat EPS with diphenhydramine or benztropine (anticholinergics). NOT dexamethasone for EPS. Dexamethasone does NOT cause EPS. Prochlorperazine 10 mg PO every 6 hours for breakthrough (NOT 25 mg PO — 25 mg is rectal dosing). Haloperidol 0.5–2 mg every 4–6 hours for breakthrough (NOT 5 mg — too high). Metoclopramide 10–20 mg every 4–6 hours. Promethazine: weak antiemetic — NOT preferred for adult cancer patients.
- Benzodiazepines (lorazepam, alprazolam): Used for ANTICIPATORY nausea and vomiting. MOA: anterograde amnesia, anxiolysis, CNS depression. Dose: lorazepam 0.5–2 mg PO the night before AND 1–2 hours before chemotherapy. Also for breakthrough CINV when anxiety is a component. NOT for delayed CINV prevention.
- Dronabinol (cannabinoid): MOA = cannabinoid CB1 receptor agonist. Used for breakthrough CINV. Correct dose: 5–10 mg capsules every 3–6 hours (NOT bedtime only). Side effects: somnolence, EUPHORIA (key distinction — megestrol does NOT cause euphoria). Oral solution has HIGHER bioavailability than capsules.
STANDARD ANTIEMETIC REGIMENS:
HEC (≥ 90% risk, e.g., cisplatin, AC):
- 3-drug regimen (Regimen A): NK1 antagonist + 5-HT3 antagonist + dexamethasone 12 mg (with NK1).
- 3-drug regimen (Regimen B): olanzapine + palonosetron + dexamethasone.
- 4-drug regimen (Regimen C): olanzapine 10 mg + NK1 antagonist + 5-HT3 antagonist + dexamethasone 12 mg.
- Delayed HEC (days 2–4):
- with oral aprepitant day 1: aprepitant 80 mg PO days 2–3 + dexamethasone 8 mg daily days 2–4.
- With fosaprepitant IV day 1: dexamethasone 8 mg daily days 2–4 ONLY (no additional aprepitant).
- With olanzapine 4-drug regimen: olanzapine 10 mg + dexamethasone 8 mg daily days 2–4. If breakthrough develops and dexamethasone stops before day 4: extend dexamethasone 8 mg daily on days 5 and 6.
MEC (30–90%):
- Without NK1 antagonist: palonosetron + dexamethasone 12 mg (palonosetron is preferred over ondansetron for MEC without NK1 antagonist).
- With NK1 antagonist: any 5-HT3 antagonist + NK1 + dexamethasone 12 mg. Olanzapine + palonosetron + dexamethasone (olanzapine cannot be given with dexamethasone alone — palonosetron must be included per guidelines). Low-risk patients (no prior CINV risk factors): consider omitting NK1 antagonist for MEC.
Low emetic risk:
- single agent — dexamethasone OR 5-HT3 antagonist OR prochlorperazine. CHOP regimen: CHOP already contains prednisone → ondansetron 24 mg PO is sufficient (no additional dexamethasone needed since steroids are part of CHOP); prednisone in regimen covers steroid component.
classified as LOW emetogenic risk. Dexamethasone before pemetrexed is given to prevent SKIN REACTIONS — not as antiemetic. No routine antiemetic prophylaxis required.
GRANISETRON TRANSDERMAL PATCH (Sancuso):
Apply 24–48 hours BEFORE chemotherapy. Releases 3.1 mg/24 hours. Can be worn up to 7 days. Ideal for multi-day regimens and patients who cannot take oral medications.
Treatment: IV normal saline hydration + bisphosphonate (zoledronic acid 4 mg IV — NOT 5 mg — 5 mg is osteoporosis dose) + calcitonin (rapid onset within 12–24 hours; tachyphylaxis after 48 hours). Pamidronate is less potent than zoledronic acid. Gallium nitrate: reserved for refractory hypercalcemia (nephrotoxic). Intranasal calcitonin is NOT effective. Signs/symptoms of hypercalcemia: nausea, vomiting, increased thirst, fatigue, CONSTIPATION (NOT diarrhea).
TUMOR LYSIS SYNDROME (TLS):
Allopurinol: prevents uric acid formation (xanthine oxidase inhibitor) — does NOT lower existing uric acid levels. Start for intermediate-risk patients. Rasburicase: rapidly converts uric acid to allantoin — use for HIGH-RISK or already elevated uric acid with renal dysfunction. Contraindicated in G6PD deficiency. Allopurinol + rasburicase CAN be used together (different mechanisms). Sodium bicarbonate urinary alkalinization: NOT currently recommended (risk of calcium-phosphate precipitation). Calcium gluconate: stabilizes cardiac membrane — does NOT lower potassium. Insulin + dextrose: drives potassium intracellularly (temporary). Sodium polystyrene sulfonate: lowers potassium via bowel cationic exchange. Calcium acetate: phosphate binder — use for hyperphosphatemia in TLS.
MUCOSITIS:
Melphalan (high-dose HSCT): cryotherapy (ice chips) during infusion significantly reduces mucositis severity — best prevention option. Sucralfate and triple mix (diphenhydramine + nystatin + lidocaine) are NOT effective for mucositis prevention. Palifermin (keratinocyte growth factor): pre- and post-conditioning for autologous HSCT with radiation — absolute risk reduction of 35% in severe mucositis, reduces duration from 9 to 3 days. Temozolomide + radiation + steroids → PJP prophylaxis with TMP-SMX or dapsone required. Discontinue PJP prophylaxis after radiation ends as long as patient is not lymphopenic.
PPI AND POSACONAZOLE INTERACTION:
Proton pump inhibitors (PPIs) decrease posaconazole and itraconazole absorption (reduces AUC by ~30%). Avoid PPIs with posaconazole. H2 blockers and antacids (except cimetidine) do NOT significantly alter posaconazole levels. Cimetidine inhibits CYP3A4 and significantly interacts with erlotinib metabolism — avoid.
ESA THERAPY: ESAs (epoetin, darbepoetin) initiation threshold: hemoglobin < 10 g/dL. Target: lowest Hb to avoid transfusion (generally 11–12 g/dL). ESAs are CONTRAINDICATED in patients receiving chemotherapy with CURATIVE intent. ESAs are also NOT indicated for patients receiving non-myelosuppressive therapy (e.g., trastuzumab is NOT myelosuppressive).
IRINOTECAN DIARRHEA:
Acute diarrhea (< 24 hours after irinotecan): cholinergic symptoms (cramping, salivation, lacrimation, rhinitis) → treat with ATROPINE. Delayed diarrhea (> 24 hours after irinotecan): treat with LOPERAMIDE. Octreotide is for refractory cases.
OPIOID PHARMACOLOGY:
Morphine 10 mg IM = 30 mg PO (chronic pain; 1:3 ratio). Opioid conversion: reduce new opioid equivalent dose by 25–50% (incomplete cross-tolerance). Methadone conversion: reduce by 75–90% (very potent, long half-life up to 60 hours, accumulation risk). Fentanyl and methadone: major CYP3A4 substrates. Hydrocodone, codeine: CYP2D6 substrates. Morphine: glucuronidation (phase II) — minimal CYP interaction. Morphine overdose: MIOSIS (pinpoint pupils) — classic sign. Opioids do NOT develop tolerance to constipation (bowel regimen required indefinitely). Morphine histamine release: NON-IgE mediated (pseudoallergic, not true Type I reaction). Tramadol: dual mechanism — weak opioid + SNRI (serotonin/norepinephrine reuptake inhibitor). Metabolized by CYP2D6 and CYP3A4. Avoid with fluoxetine/paroxetine (CYP2D6 inhibitors — increased tramadol levels + serotonin syndrome risk). Tamoxifen VTE risk: long-distance flights increase thrombosis risk. Tamoxifen does NOT cause hypolipidemia (it HAS hypolipidemic effects). Tamoxifen 10-year therapy: high-risk patients benefit from extended therapy.
EXTRAVASATION
Extravasation: Anthracyclines are severe vesicants managed with Dexrazoxane (preferred) and cold compresses. Vinca alkaloids are managed with Hyaluronidase and warm compresses.
Pulmonary Toxicity: Bleomycin carries a high risk for pulmonary dysfunction; baseline and periodic PFTs (DLCO) may be necessary, and the drug is often omitted if toxicity develops.
Viral Reactivation: All patients receiving anti-CD20 antibodies (Rituximab, Obinutuzumab) must be screened for Hepatitis B due to high reactivation risk
PRACTICE QUESTIONS — CINV AND SUPPORTIVE CARE
True or False: All 5-HT3 receptor antagonists are equivalent for the prevention of acute emesis from highly emetogenic chemotherapy.
A. True
B. False
Explanation: While first-generation 5-HT3 antagonists (ondansetron, granisetron, dolasetron) are generally considered interchangeable at equipotent doses, palonosetron — a second-generation agent — is NOT equivalent to first-generation agents. Palonosetron has a longer half-life (~40 hours) and unique allosteric and facilitative binding to the 5-HT3 receptor that provides superior efficacy in preventing BOTH acute and delayed CINV. Meta-analyses have demonstrated palonosetron superiority over first-generation agents. Notably, when an NK1 antagonist is also used, palonosetron and ondansetron are considered interchangeable — but without an NK1 antagonist (particularly for MEC), palonosetron is the preferred 5-HT3 agent.
[/expand]Which one of the following antiemetics is NOT known to cause extrapyramidal symptoms?
A. Metoclopramide
B. Dexamethasone
C. Droperidol
D. Promethazine
Explanation: Extrapyramidal symptoms (EPS) — including tremor, restlessness, dystonia, and oculogyric crisis — are caused by medications that block dopamine receptors. Metoclopramide (option A) is a dopamine antagonist — EPS risk especially at higher doses; requires diphenhydramine or benztropine for treatment. Droperidol (option C) is a butyrophenone dopamine antagonist — EPS is a known class effect. Promethazine (option D) is a phenothiazine dopamine antagonist — causes dystonia and akathisia (EPS types). Dexamethasone (option B) is a corticosteroid — its side effects are hyperglycemia, insomnia, and dyspepsia — it has NO dopaminergic activity and does NOT cause EPS.
[/expand]JJ is a 66-year-old woman with breast cancer receiving her first cycle of paclitaxel. Sixty minutes before chemotherapy, she receives a hypersensitivity prevention regimen of dexamethasone, ranitidine, and diphenhydramine. What antiemetic regimen do you recommend before paclitaxel?
A. Ondansetron 8 mg IV
B. Fosaprepitant 150 mg IV
C. Ondansetron 8 mg IV plus fosaprepitant 150 mg IV
D. No additional premedications needed
Explanation: Paclitaxel is classified as LOW emetic risk (10–30% incidence without prophylaxis). For low-risk chemotherapy, guidelines recommend a single antiemetic agent — such as dexamethasone alone or a 5-HT3 antagonist alone. JJ has ALREADY received dexamethasone as part of her hypersensitivity prevention regimen — this single agent provides adequate CINV prophylaxis for low-risk chemotherapy. Adding ondansetron or fosaprepitant (options A, B, C) represents over-treatment for the low emetogenic risk of paclitaxel. She may receive a PRN antiemetic prescription for home use if desired.
[/expand]ST is a 48-year-old male with colorectal cancer starting FOLFOX (fluorouracil, leucovorin, oxaliplatin). No history of nausea/vomiting. He drinks 2 cans of beer daily. Which antiemetic regimen is most appropriate?
- Ondansetron 16 mg IV × 1 and dexamethasone 12 mg IV × 1 on day 1 followed by dexamethasone 8 mg PO daily on days 2–3
- Olanzapine 10 mg PO × 1 and dexamethasone 12 mg IV × 1 on day 1 followed by olanzapine 10 mg PO daily on days 2–3
- Palonosetron 0.25 mg IV × 1 and dexamethasone 12 mg IV × 1 on day 1 followed by dexamethasone 8 mg PO daily on days 2–3
- Fosaprepitant 150 mg IV × 1 and dexamethasone 12 mg IV × 1 on day 1 followed by dexamethasone 8 mg PO daily on days 2–3
Explanation: FOLFOX contains oxaliplatin — classified as MEC (30–90% risk). ST has two factors that REDUCE his CINV risk: no prior nausea/vomiting history AND daily alcohol use (regular alcohol use is protective against CINV). Given his lower risk profile, an NK1 antagonist is NOT necessary. For MEC without an NK1 antagonist, palonosetron is the PREFERRED 5-HT3 antagonist (superior to ondansetron for delayed CINV control due to longer half-life and unique binding). Dexamethasone 12 mg day 1 + 8 mg days 2–3 covers delayed phase from oxaliplatin. Ondansetron (option A) — acceptable but not preferred when NK1 is omitted. Olanzapine + dexamethasone without palonosetron (option B) — incorrect; olanzapine must be combined with palonosetron per guidelines. Fosaprepitant without a 5-HT3 antagonist (option D) — incomplete regimen; NK1 antagonists must be paired with a 5-HT3 antagonist.
[/expand]Which one of the following agents is a neurokinin-1 (NK1) receptor antagonist?
A. Dronabinol
B. Fosaprepitant
C. Olanzapine
D. Palonosetron
Explanation: Fosaprepitant is an IV prodrug rapidly converted to aprepitant by phosphatase enzymes — it is an NK1 receptor antagonist that blocks substance P from binding to NK1 receptors in the brain, preventing both acute and delayed CINV. Dronabinol (option A) is a cannabinoid targeting CB1 receptors. Olanzapine (option C) is an atypical antipsychotic blocking D2, 5-HT2/3, histaminergic, and muscarinic receptors — not an NK1 antagonist. Palonosetron (option D) is a second-generation 5-HT3 (serotonin) receptor antagonist.
[/expand]SS is a 55-year-old breast cancer patient receiving her fourth cycle of cyclophosphamide + doxorubicin. Before chemotherapy begins, she rushes to the bathroom and vomits. Why did she have this vomiting episode?
A. SS is exhibiting anticipatory nausea from her motion sickness history
B. SS is constipated from anthracycline-induced neurotoxicity
C. SS is experiencing delayed emesis from her last cycle three weeks ago
D. SS developed anticipatory vomiting from poor antiemetic control with previous cycles
Explanation: This is a classic presentation of ANTICIPATORY nausea and vomiting — a conditioned reflex triggered by sensory cues (the sights, sounds, smells of the treatment environment) BEFORE chemotherapy is administered. The primary and strongest cause of anticipatory CINV is POOR EMETIC CONTROL in prior chemotherapy cycles. SS is now on cycle 4 of a HEC (AC) regimen — her body has developed a learned emetic response. Option A — motion sickness history is a RISK FACTOR for CINV in general, but the specific trigger here is the conditioned response from prior poor control. Option B — anthracyclines cause cardiotoxicity, not the neurotoxicity-driven constipation seen with vincristine. Option C — delayed emesis occurs 1–5 days after chemotherapy; a 3-week gap is far beyond the delayed emesis window.
[/expand]When dexamethasone is added to a 5-HT3 receptor antagonist, how much additional antiemetic protection is gained?
A. None
B. 5%
C. 20%
D. 80%
Explanation: Clinical data and meta-analyses consistently show that adding dexamethasone to a 5-HT3 antagonist provides approximately 20% additional antiemetic protection for acute emesis. For example, in a trial using granisetron ± dexamethasone: complete protection from vomiting was 93% with the combination versus 71–72% with either agent alone. This approximately 20% improvement is why all major guidelines (ASCO, NCCN, MASCC) mandate dexamethasone as a core component of multi-drug antiemetic regimens for both HEC and MEC. The 20% figure represents the marginal additional benefit of adding dexamethasone — not the total response rate of the combination.
[/expand]If a patient develops anticipatory nausea and vomiting from poor antiemetic control, which agent should be started?
A. Dronabinol
B. Lorazepam
C. Ondansetron
D. Promethazine
Explanation: Anticipatory CINV is a psychologically conditioned response requiring agents that break the conditioned reflex. Benzodiazepines (lorazepam) are the preferred pharmacological class — they work through anterograde amnesia (helping the patient forget negative treatment stimuli), anxiolysis (reducing anxiety that contributes to the emetic response), and CNS depression (reducing emetic signaling pathways). Dosing: lorazepam 0.5–2 mg PO the night before AND 1–2 hours before chemotherapy. Dronabinol (option A) is for breakthrough CINV — not anticipatory. Ondansetron (option C) targets serotonin receptors for acute CINV — does not address the psychologically conditioned reflex of anticipatory emesis. Promethazine (option D) is a weak antiemetic not preferred for adult cancer patients.
[/expand]IK is a 55-year-old male receiving cisplatin + etoposide for SCLC. His antiemetic regimen included ondansetron, aprepitant, and dexamethasone. After his first cycle, he complained of vomiting × 3 episodes starting 48 hours after chemotherapy. What change to his antiemetic regimen would you make for cycle 2?
A. No change is necessary
B. Change ondansetron to palonosetron
C. Add granisetron to the current regimen
D. Increase dexamethasone from 12 to 20 mg IV
Explanation: IK has DELAYED CINV (vomiting starting 48 hours after chemotherapy — > 24 hours = delayed phase). Palonosetron — the second-generation 5-HT3 antagonist — has superior efficacy over first-generation agents (ondansetron, granisetron) in preventing delayed CINV due to its longer half-life and unique allosteric binding. Switching from ondansetron to palonosetron specifically targets the delayed phase failure. No change (option A) is inappropriate — he experienced 3 vomiting episodes, indicating inadequate prophylaxis. Adding granisetron (option C) — granisetron is the same pharmacological class as ondansetron (first-generation 5-HT3 RA) — no additional delayed protection. Increasing dexamethasone to 20 mg (option D) — incorrect because aprepitant inhibits CYP3A4 → INCREASES dexamethasone concentration; increasing the dose could cause excessive steroid toxicity. The dose is appropriately reduced to 12 mg with aprepitant.
[/expand]Which of the following statements is true regarding antiemetic agents?
A. Both palonosetron and rolapitant have long half-lives and are thus more effective at preventing delayed nausea/vomiting
B. Dronabinol capsules have higher bioavailability than dronabinol oral solution
C. All NK1 antagonists (fosaprepitant, aprepitant, netupitant, fosnetupitant, and rolapitant) inhibit the metabolism of dexamethasone
D. Aprepitant inhibits warfarin metabolism via CYP2C9 and can lead to supratherapeutic INRs
Explanation: Palonosetron (5-HT3 antagonist) has a half-life of ~40 hours — much longer than first-generation agents — providing delayed phase efficacy. Rolapitant (NK1 antagonist) has an extraordinarily long half-life (~180 hours oral, ~76 days IV) — administered once before chemotherapy for complete delayed phase coverage. Option B is incorrect — dronabinol ORAL SOLUTION has HIGHER bioavailability than the capsules. Option C is incorrect — ROLAPITANT is the EXCEPTION among NK1 antagonists; it does NOT inhibit CYP3A4 and therefore does NOT require dexamethasone dose reduction. Option D is incorrect — aprepitant INDUCES CYP2C9, which INCREASES warfarin metabolism → DECREASES INR (subtherapeutic, NOT supratherapeutic). This occurs approximately 7–10 days after aprepitant.
[/expand]TJ is a 72-year-old male with stage IV NSCLC, 45 pack-year smoking history, and drinks 4–5 beers per day. He will receive chemotherapy.
Which of the factors below are associated with a REDUCED risk of emetogenic potential for TJ?
A. Age, gender, alcohol history
B. Gender, alcohol history, smoking history
C. Alcohol history, smoking history, age
D. Smoking history, age, gender
Explanation: Factors that REDUCE CINV risk: Older age (TJ is 72 — older patients have lower CINV risk), male sex (males have lower CINV risk than females), regular/heavy alcohol consumption (TJ drinks 4–5 beers daily — alcohol use ≥ 5 drinks/week is protective). Smoking has NOT been identified as having a significant impact (positive or negative) on CINV risk — it is neither a risk factor nor a protective factor. Therefore, smoking is NOT included in option A — making option A the only combination of all three proven protective factors.
[/expand]JS is a 55-year-old woman with stage II NSCLC receiving cisplatin 75 mg/m² + pemetrexed 500 mg/m² on day 1. PMH: depression, motion sickness, and morning sickness during pregnancy. She is a social drinker who stopped smoking 15 years ago.
Besides being female with a history of motion sickness and morning sickness, what other risk factor does JS have for increased CINV?
A. Social drinker
B. Non-smoker
C. Depression
D. Patient age
Explanation: Psychological conditions such as depression and high anxiety are established risk factors for increased CINV susceptibility. Social drinking (option A) — casual drinking without heavy/chronic use does NOT significantly impact CINV risk either way. Non-smoker (option B) — smoking history has no significant impact on CINV risk. Patient age alone (option D) is not the key factor here — age < 50 increases risk, but the scenario's primary identified factor is her psychological history. The question specifically asks for a factor BEYOND her known female sex, motion sickness, and morning sickness history — depression fits this role.
[/expand]In addition to fosaprepitant 150 mg IV on day 1, JS should receive which of the following medications for the prevention of acute nausea and vomiting?
A. Palonosetron 0.25 mg IV plus dexamethasone 20 mg PO
B. Palonosetron 0.25 mg IV plus dexamethasone 12 mg PO
C. Ondansetron 4 mg IV plus dexamethasone 20 mg PO
D. Ondansetron 4 mg IV plus dexamethasone 12 mg PO
Explanation: JS is receiving cisplatin — HEC (> 90% risk). A 3-drug regimen is required: NK1 antagonist (already receiving fosaprepitant 150 mg IV) + 5-HT3 antagonist + dexamethasone. Palonosetron 0.25 mg IV is a preferred 5-HT3 agent. Dexamethasone dose MUST be 12 mg (NOT 20 mg) when given with an NK1 antagonist — fosaprepitant inhibits CYP3A4 → increases dexamethasone concentration → dose reduction required to prevent excessive steroid toxicity. Options A and C use 20 mg dexamethasone — incorrect with NK1 antagonist. Options C and D use ondansetron 4 mg — incorrect for HEC (ondansetron dose for HEC is 8 mg or 0.15 mg/kg; 4 mg is insufficient).
[/expand]For the prevention of delayed nausea and vomiting in JS (receiving fosaprepitant day 1 for cisplatin), she should receive:
- Dexamethasone 8 mg PO daily on days 2 to 4
- Dexamethasone 8 mg PO daily on days 2–4 plus ondansetron 8 mg PO daily on days 2–4
- Aprepitant 80 mg PO daily on days 2–3 plus dexamethasone 8 mg PO daily on days 2–4
- Aprepitant 80 mg PO daily on days 2–3 plus dexamethasone 8 mg PO daily on days 2–4 plus ondansetron 8 mg PO daily on days 2–4
Explanation: When FOSAPREPITANT 150 mg IV is given on day 1, it provides COMPLETE NK1 coverage for the ENTIRE CYCLE — no additional aprepitant is needed on days 2–3 (this is different from oral aprepitant 125 mg day 1, which DOES require 80 mg on days 2–3). After fosaprepitant, the delayed phase regimen is dexamethasone 8 mg daily on days 2–4 ONLY. 5-HT3 antagonists (ondansetron) — NOT recommended for delayed phase prevention of HEC per ASCO/MASCC guidelines. Options C and D incorrectly add oral aprepitant after fosaprepitant. Options B and D incorrectly add ondansetron for the delayed phase.
[/expand]On day 5, JS calls the clinic complaining of nausea and vomiting. She has been using prochlorperazine 10 mg PO Q6H without significant improvement. What would be an acceptable addition to her antiemetic regimen in lieu of prochlorperazine?
A. Metoclopramide 10 mg PO every 6 hours
B. Haloperidol 5 mg PO every 6 hours
C. Dronabinol 5 mg PO at bedtime
D. Aprepitant 80 mg PO daily
Explanation: JS has breakthrough emesis that is not responding to prochlorperazine. The principle is to add an agent from a DIFFERENT drug class. Metoclopramide (benzamide dopamine antagonist) provides a different mechanism from prochlorperazine (phenothiazine dopamine antagonist) — acceptable class switch. Haloperidol (option B) is an acceptable rescue agent, but the dose of 5 mg is TOO HIGH — correct dose is 0.5–2 mg every 4–6 hours. Dronabinol (option C) — incorrect schedule; dronabinol for breakthrough must be dosed every 3–6 hours, NOT bedtime only. Aprepitant (option D) — re-starting or extending NK1 antagonists for breakthrough emesis is NOT supported by clinical data and NOT recommended by guidelines.
[/expand]What would you add to JS's next cycle of chemotherapy to prevent delayed nausea and vomiting, given she developed breakthrough symptoms on day 5?
A. Metoclopramide 10 mg PO daily
B. Dexamethasone 8 mg PO daily days 5 and 6
C. Dronabinol 5 mg PO at bedtime
D. Aprepitant 80 mg PO daily
Explanation: JS developed breakthrough symptoms on day 5 — immediately after her 4-day dexamethasone course (days 1–4) ended. The targeted adjustment is to EXTEND the dexamethasone course by 2 additional days (days 5 and 6) to close the gap when her nausea broke through. This directly addresses the timing of her symptoms without adding different drug classes. Metoclopramide once daily (option A) is insufficient — metoclopramide requires dosing every 6 hours for prophylactic efficacy. Dronabinol (option C) is not effective for delayed-phase prevention. Aprepitant beyond day 3 (option D) has no clinical data supporting its use and is NOT recommended for breakthrough or delayed phase management.
[/expand]JS (second version, 60-year-old, high-risk patient with prior poor CINV control from AC chemotherapy at age 29) is receiving cisplatin + pemetrexed. In addition to aprepitant 130 mg IV day 1, she should receive which acute antiemetic regimen?
A. Palonosetron 0.25 mg IV + dexamethasone 12 mg PO + olanzapine 5 mg PO
B. Palonosetron 0.25 mg IV + dexamethasone 12 mg PO
C. Ondansetron 8 mg IV + dexamethasone 20 mg PO + olanzapine 5 mg PO
D. Ondansetron 4 mg IV + dexamethasone 20 mg PO
Explanation: JS has multiple high-risk factors for CINV: female, history of motion sickness, morning sickness, AND prior significant nausea with chemotherapy (strongest predictor for future CINV). For HEC with multiple high-risk factors, a FOUR-DRUG regimen is now the current standard: NK1 antagonist (already receiving aprepitant 130 mg IV) + 5-HT3 antagonist (palonosetron preferred) + dexamethasone 12 mg (dose-reduced due to NK1 antagonist) + olanzapine 5–10 mg. Option B is only a 3-drug regimen — inadequate for high-risk HEC patient. Option C uses dexamethasone 20 mg — incorrect when NK1 antagonist is present. Option D uses ondansetron 4 mg — insufficient dose for HEC.
[/expand]For delayed phase prevention in JS (four-drug regimen, high-risk cisplatin patient), she should receive:
A. Dexamethasone 8 mg PO daily on days 2 to 4
B. Dexamethasone 8 mg PO daily on days 2–4 plus olanzapine 5 mg PO daily on days 2–4
C. Aprepitant 80 mg PO daily on days 2–3 plus dexamethasone 8 mg PO daily on days 2–4
D. Aprepitant 80 mg PO daily on days 2–3 plus dexamethasone 8 mg PO daily on days 2–4 plus ondansetron 8 mg PO daily on days 2–4
Answer: B. Dexamethasone 8 mg PO daily on days 2–4 plus olanzapine 5 mg PO daily on days 2–4
Explanation: For the four-drug HEC regimen (including olanzapine day 1), updated ASCO and NCCN guidelines recommend continuing BOTH olanzapine (5–10 mg) AND dexamethasone (8 mg) on days 2–4 for optimal delayed CINV control. Since JS received aprepitant 130 mg IV (IV formulation) on day 1, no additional NK1 antagonist doses are needed on days 2–3 (IV provides complete cycle coverage). Option A omits olanzapine — incomplete 4-drug delayed phase regimen. Options C and D add oral aprepitant after IV administration — unnecessary. Option D also adds ondansetron for delayed phase — not recommended per ASCO/MASCC guidelines.
[/expand]A 62-year-old male receives cisplatin + etoposide for SCLC with palonosetron + fosaprepitant + dexamethasone day 1, and dexamethasone for delayed emesis. The following day he calls complaining of one episode of vomiting and moderate nausea. What therapy would you suggest?
A. Ondansetron
B. Aprepitant
C. Prochlorperazine
D. No intervention needed
Explanation: This patient has BREAKTHROUGH CINV. The key principle is to use an agent from a DIFFERENT class than those already used prophylactically. He already received: palonosetron (5-HT3 antagonist — class used), fosaprepitant (NK1 antagonist — class used), dexamethasone (corticosteroid — class used). Prochlorperazine is a phenothiazine dopamine receptor antagonist — a DIFFERENT class — appropriate for breakthrough rescue. Ondansetron (option A) — same 5-HT3 class as palonosetron already received; not appropriate. Aprepitant (option B) — fosaprepitant 150 mg already provides complete NK1 coverage; additional aprepitant is not recommended. No intervention (option D) — breakthrough emesis requires active management.
[/expand]Which antiemetic regimen is recommended before CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy?
A. Prochlorperazine 10 mg PO
B. Ondansetron 24 mg PO
C. Dexamethasone 20 mg PO
D. Metoclopramide 30 mg PO
Explanation: CHOP contains doxorubicin + cyclophosphamide — this AC combination is classified as HEC (> 90% risk). A 5-HT3 antagonist is a mandatory component. Ondansetron 24 mg PO (range 16–24 mg) is the appropriate dose for HEC. CRITICAL DISTINCTION: CHOP ALREADY CONTAINS PREDNISONE as part of the chemotherapy regimen. Guidelines specifically state that prednisone in a chemotherapy regimen should NOT be dose-reduced or schedule-altered — it counts as the corticosteroid component. Therefore, the ADDITION of dexamethasone is NOT necessary (prednisone covers steroid coverage) — making the 5-HT3 antagonist the primary additional agent needed. Option C (dexamethasone 20 mg PO) — while dexamethasone is standard for HEC, CHOP already contains prednisone; adding high-dose dexamethasone on top of the regimen's prednisone would be excessive corticosteroid exposure. Option A and D — prochlorperazine and metoclopramide are insufficient for HEC primary prophylaxis.
[/expand]ZK is a 62-year-old man with lung adenocarcinoma and history of hemoptysis receiving his first cycle of cisplatin + paclitaxel. Which antiemetic regimen would be most appropriate for ZK before day 1 of chemotherapy?
A. Aprepitant 125 mg PO + ondansetron 16 mg PO + dexamethasone 12 mg PO
B. Aprepitant 125 mg PO + metoclopramide 20 mg PO + dexamethasone 12 mg PO
C. Ondansetron 16 mg PO + metoclopramide 20 mg PO D.
Ondansetron 16 mg PO + prochlorperazine 10 mg PO
Explanation: Cisplatin is HEC — requires a 3-drug regimen: NK1 antagonist + 5-HT3 antagonist + dexamethasone. Aprepitant 125 mg (day 1 dose) is correct. Ondansetron 16 mg PO is an appropriate HEC dose. Dexamethasone is 12 mg (not 20 mg) because aprepitant inhibits CYP3A4 → increases dexamethasone levels → dose reduction required. Options B, C, D: metoclopramide and prochlorperazine are LOW-POTENCY dopamine antagonists — insufficient for HEC acute prevention. Option C and D omit dexamethasone — an essential component. Note: ZK has hemoptysis — bevacizumab would be contraindicated (squamous cell histology and hemoptysis), but this patient has adenocarcinoma; hemoptysis does not affect antiemetic selection.
[/expand]DM is a 32-year-old female with breast cancer on AC (doxorubicin/cyclophosphamide). First cycle: aprepitant 125 mg PO + palonosetron 0.25 mg IV + dexamethasone 12 mg IV day 1; aprepitant 80 mg PO days 2–3; dexamethasone 8 mg PO days 2–4. She is still experiencing severe nausea/vomiting one week after chemotherapy. Which treatment is most appropriate for DM at this time?
A. Prochlorperazine 25 mg PO Q6H
B. Haloperidol 5 mg PO Q6H
C. Ondansetron 8 mg PO Q8H
D. Dronabinol capsules 5 mg PO 4 times daily
Explanation: DM has BREAKTHROUGH CINV requiring an agent from a DIFFERENT class. Her prophylaxis included NK1 antagonist (aprepitant), 5-HT3 antagonist (palonosetron), and corticosteroid (dexamethasone) — all three major classes used. Dronabinol (cannabinoid) provides a different mechanism — CB1 receptor agonism. Correct dose: 5–10 mg capsules every 4–6 hours (4 times daily = every 6 hours, within guideline range). Option A — prochlorperazine 25 mg PO is incorrect dosing; oral prochlorperazine is 10 mg every 6 hours (25 mg is rectal dosing). Option B — haloperidol 5 mg is too high; correct breakthrough dose is 0.5–2 mg every 4–6 hours. Option C — ondansetron is the same 5-HT3 class as palonosetron she already received — not appropriate for breakthrough rescue.
[/expand]JH is receiving high-dose cisplatin 100 mg/m² with palonosetron + aprepitant + dexamethasone before the dose. Which antiemetic prescription should JH receive before going home?
- Aprepitant 80 mg PO daily for 2 days + dexamethasone 20 mg PO daily for 2 days
- Aprepitant 80 mg PO daily for 2 days + dexamethasone 8 mg PO daily for 3 days
- Prochlorperazine 10 mg PO four times a day PRN
- Ondansetron 8 mg PO TID for 3 days
Explanation: JH received oral aprepitant 125 mg (implied from "aprepitant") on day 1 — oral aprepitant requires continuation: 80 mg PO on days 2 AND 3 (this is different from IV fosaprepitant which requires no additional doses). Dexamethasone for delayed phase with cisplatin: 8 mg PO daily on days 2, 3, and 4 (3-day course). Dose remains 8 mg (not 20 mg) because aprepitant continues to inhibit CYP3A4. 5-HT3 antagonists (ondansetron — option D) are NOT recommended for delayed HEC prophylaxis per guidelines. Prochlorperazine PRN (option C) is for breakthrough — not standard HEC delayed prophylaxis. Option A uses dexamethasone 20 mg — incorrect when NK1 antagonist is present.
[/expand]AY is a 69-year-old female on IV paclitaxel + carboplatin for NSCLC. First cycle: ondansetron 8 mg IV + dexamethasone 20 mg IV day 1; dexamethasone 8 mg PO daily days 2–4. She is still experiencing severe nausea/vomiting on day 5. Which treatment is most appropriate for AY at this time?
A. Aprepitant 80 mg PO daily
B. Ondansetron 8 mg PO Q8H
C. Promethazine 10 mg PO Q6H
D. Olanzapine 5 mg PO daily
Explanation: AY has breakthrough CINV. Her prophylaxis included: ondansetron (5-HT3 class used) and dexamethasone (corticosteroid class used). Olanzapine works through a DIFFERENT multi-receptor mechanism (D2, 5-HT2/3, histaminergic, muscarinic blockade) — appropriate for breakthrough. NCCN recommends olanzapine 5–10 mg daily as needed for breakthrough management. Aprepitant (option A) — NK1 antagonists are not recommended for active breakthrough management (no clinical data supporting this use). Ondansetron (option B) — same 5-HT3 class as already-used ondansetron; not recommended for breakthrough rescue of the same class. Promethazine 10 mg Q6H (option C) — incorrect dosing; promethazine should be 12.5–25 mg Q4–6H; promethazine is also a WEAK antiemetic not preferred in adult cancer patients.
[/expand]Which of the following are risk factors for chemotherapy-induced nausea and vomiting?
A. Female sex
B. Patients younger than 50 years of age
C. Minimal or no alcohol consumption
D. All of the above
Explanation: All three listed options are established patient-specific CINV risk factors. Female sex increases CINV susceptibility compared to males. Age younger than 50 (some sources specify ≤ 40) — younger patients have higher CINV risk; older patients have lower risk. Minimal or no alcohol consumption — heavy alcohol use (≥ 5 drinks/week or ≥ 100 g/day chronically) is PROTECTIVE against CINV; therefore, minimal/no alcohol intake means this protective factor is absent, increasing risk. Additional risk factors: history of motion sickness, pregnancy-related emesis, prior chemotherapy-related emesis, and high anxiety levels.
[/expand]LJ is a 44-year-old man scheduled to receive CHOP for non-Hodgkin's lymphoma. He does not like taking pills and prefers non-oral forms. Which 5-HT3 antiemetic regimen would be preferred?
A. Ondansetron 8 mg oral disintegrating tablet before CHOP
B. Granisetron transdermal patch to be applied the day before chemotherapy for up to 7 days
C. Ondansetron 8 mg IV as a single dose
D. Dolasetron 100 mg oral tablet before CHOP
(Note: In the source material two different correct answers appear for the same question — one source says B [granisetron patch], another says C [ondansetron IV]. For exam purposes, both B and C are defensible non-oral routes, but the granisetron patch provides more sustained coverage for multi-day delayed emesis risk and is the ideal answer for a patient who specifically prefers non-pill options with multi-day coverage.)
Explanation: CHOP is HEC — requiring a potent 5-HT3 antagonist as part of prophylaxis. LJ specifically avoids oral pills. Granisetron transdermal patch (Sancuso) is a non-oral option: applied 24–48 hours before chemotherapy, releases 3.1 mg/24 hours, effective for up to 7 days — covers both acute and delayed phases. Ondansetron ODT (option A) — dissolves in mouth without water but is still taken like a pill; also, 8 mg is typically insufficient for HEC. Ondansetron IV (option C) — avoids pills but provides only single-dose acute coverage without sustained delayed phase protection. Dolasetron oral tablet (option D) — this is an oral pill, directly against the patient's stated preference.
[/expand]MJ is a 55-year-old male receiving cisplatin + etoposide for SCLC. His regimen included palonosetron + aprepitant + dexamethasone. He returns the following day with nausea and vomiting. What do you recommend for his treatment of breakthrough nausea and vomiting?
A. Ondansetron 8 mg IV
B. One liter normal saline plus ondansetron 8 mg IV
C. One liter normal saline plus haloperidol 2 mg IV
D. Promethazine 25 mg PO
Explanation: MJ has breakthrough CINV with active vomiting. Two components are needed: (1) IV hydration — one liter normal saline to address/prevent dehydration from active vomiting; (2) antiemetic from a DIFFERENT class than prophylaxis used. MJ's prophylaxis included palonosetron (5-HT3 class), aprepitant (NK1 class), and dexamethasone (corticosteroid class). Haloperidol (butyrophenone dopamine antagonist) is from a different class — appropriate at 0.5–2 mg every 4–6 hours IV. Ondansetron (options A and B) — same 5-HT3 class as palonosetron he already received; not recommended for same-class breakthrough rescue. Promethazine PO (option D) — oral route is NOT preferred for active breakthrough vomiting (IV/rectal preferred); promethazine is also a weak antiemetic not preferred in adult cancer patients.
[/expand]IK (62-year-old, cisplatin + etoposide, 3 vomiting episodes starting 48 hours after chemotherapy) — what type of emesis is this, and which agent is responsible?
A. Acute emesis from etoposide
B. Delayed emesis from etoposide
C. Acute emesis from cisplatin
D. Delayed emesis from cisplatin
Explanation: Vomiting beginning 48 hours after chemotherapy is DELAYED CINV (> 24 hours post-treatment). Cisplatin is the classic prototype agent for DELAYED emesis — peaks at 48–72 hours post-administration and can last 6–7 days. Etoposide alone is classified as LOW emetogenic risk — it is unlikely to produce significant acute or delayed emesis on its own. The combination puts the cisplatin as the culprit for delayed CINV.
[/expand]JK is a 65-year-old male receiving cisplatin + etoposide for SCLC. After repeated cycles with breakthrough CINV, he is at a grocery store one week later, sees his chemotherapy nurse, and begins to vomit. What type of vomiting is JK experiencing?
A. Acute emesis
B. Delayed emesis
C. Breakthrough emesis
D. Anticipatory emesis
Explanation: JK's vomiting was triggered by SEEING his chemotherapy nurse — a sensory cue associated with his prior treatment environment. This is the definition of ANTICIPATORY CINV: a Pavlovian (conditioned) response where a patient develops emesis in response to cues associated with chemotherapy, even when no chemotherapy is being administered. The cause: repeated poor emesis control during chemotherapy cycles created a conditioned response. The sight of the nurse (associated with prior vomiting episodes) was sufficient to trigger vomiting.
[/expand]Which of the following drugs is correctly matched to its side effects?
A. Granisetron: headache, constipation
B. Olanzapine: diarrhea, drowsiness
C. Lorazepam: hyperglycemia, dyspepsia
D. Dexamethasone: drowsiness, QTc prolongation
Explanation:
- 5-HT3 antagonists (granisetron, ondansetron) consistently cause headache and constipation — these are classic, well-documented toxicities. They may also transiently elevate liver function tests. QTc prolongation is associated with first-generation 5-HT3 agents (ondansetron, granisetron) but is not on palonosetron's label.
- Option B incorrect — olanzapine causes CONSTIPATION (not diarrhea) and drowsiness/somnolence.
- Option C is incorrect — hyperglycemia and dyspepsia are DEXAMETHASONE toxicities, not lorazepam. Lorazepam causes sedation, amnesia, and hypotension. Option D incorrect — dexamethasone causes INSOMNIA (not drowsiness) and hyperglycemia. QTc prolongation is associated with olanzapine and haloperidol, not dexamethasone.
PT is a 58-year-old male with squamous cell carcinoma of the tongue presenting with symptomatic hypercalcemia. ECG shows shortened QT interval. Calcium = 12.6 mg/dL, albumin = 3.0 g/dL, SCr = 1.5 mg/dL. Which is the most appropriate first-line treatment for hypercalcemia of malignancy?
A. Normal saline + pamidronate 60 mg IV + gallium nitrate 200 mg/m² IV
B. Normal saline + zoledronic acid 5 mg IV + calcitonin
C. Normal saline + zoledronic acid 4 mg IV + calcitonin
D. Normal saline + gallium nitrate 200 mg/m² IV + calcitonin
Explanation: Standard hypercalcemia of malignancy treatment: IV hydration (NS to dilute calcium and increase renal excretion) + bisphosphonate (zoledronic acid preferred over pamidronate — more potent with similar toxicity) + calcitonin (for symptomatic patients — rapid onset within 12–24 hours; tachyphylaxis occurs after ~48 hours). Zoledronic acid dose is 4 mg IV — NOT 5 mg. Zoledronic acid 5 mg (Reclast) is approved for OSTEOPOROSIS — NOT hypercalcemia. Gallium nitrate (options A and D) is reserved for REFRACTORY hypercalcemia — carries nephrotoxicity risk. Calcitonin is needed here because PT is SYMPTOMATIC (ECG changes) — requires faster-acting agent while bisphosphonate takes 2–7 days to reach nadir calcium.
[/expand]Which of the following adverse events is NOT attributed to 5-HT3 receptor antagonists?
A. Constipation
B. Headache
C. Diarrhea
D. Hypertension
Explanation: 5-HT3 receptor antagonists are heavily concentrated in the GI tract and CNS. Their GI effects include both constipation AND diarrhea (because serotonin normally modulates GI motility — blocking it can cause either). Headache is a well-documented CNS adverse effect. Hypertension is NOT an adverse effect of 5-HT3 receptor antagonists — they do not have significant cardiovascular effects on blood pressure (though QTc prolongation can occur with some first-generation agents). Hypertension is associated with bevacizumab, VEGF TKIs (axitinib, pazopanib), and some other oncology agents — not 5-HT3 antagonists.
[/expand]Which of the following is the most appropriate first-line treatment modality for hypercalcemia?
(Signs/symptoms consideration: BK is a 56-year-old female with breast cancer presenting with diarrhea, nausea and vomiting, increased thirst, and fatigue.)
Which symptoms are consistent with hypercalcemia?
A. Nausea and vomiting, increased thirst, fatigue
B. Fatigue, diarrhea, nausea and vomiting
C. Increased thirst, fatigue, diarrhea
D. Diarrhea, nausea and vomiting, increased thirst
Answer: A. Nausea and vomiting, increased thirst, fatigue
Explanation: Classic hypercalcemia symptoms involve GI, renal, neurologic, and cardiac systems. GI symptoms of hypercalcemia: nausea, vomiting, anorexia, and CONSTIPATION — NOT diarrhea. Renal symptoms: polyuria, polydipsia (increased thirst). Neurologic: fatigue, weakness, confusion, lethargy. Cardiac: shortened QT interval, arrhythmias. Diarrhea is NOT a symptom of hypercalcemia — its presence in this patient is a distractor. Options B, C, and D all include diarrhea — incorrect. Option A correctly identifies the three hypercalcemia-consistent symptoms while excluding diarrhea.
[/expand]Which agent can be administered to reduce the extrapyramidal side effects of metoclopramide?
A. Diphenhydramine
B. Promethazine
C. Dexamethasone
D. Dronabinol
Explanation: Metoclopramide causes EPS by blocking dopamine receptors, leading to excess acetylcholine activity. EPS include: pill-rolling tremor, muscular spasms of the neck, oculogyric crisis, and motor restlessness (akathisia). Treatment: drug cessation + ANTICHOLINERGIC agent. Diphenhydramine and benztropine are anticholinergics that reduce the excess acetylcholine activity driving EPS. Promethazine (option B) is a dopamine antagonist itself — it would WORSEN EPS risk. Dexamethasone (option C) is a corticosteroid — no role in treating EPS. Dronabinol (option D) is a cannabinoid — not used for EPS.
[/expand]A patient is beginning dexamethasone for delayed emesis prevention. What should be discussed with the patient about dexamethasone?
A. You may experience high blood sugar
B. You may experience low blood pressure
C. Watch out for easy bruising
D. Weight loss is a potential problem
Explanation: Corticosteroids including dexamethasone stimulate hepatic gluconeogenesis and decrease peripheral glucose utilization → HYPERGLYCEMIA. This is the primary and most important counseling point for dexamethasone use. Diabetic patients require close glucose monitoring during and after corticosteroid use. Low blood pressure (option B) — dexamethasone typically causes FLUID RETENTION and hypertension (not low blood pressure). Easy bruising (option C) — while steroids can cause skin thinning with long-term use, this is not the most immediate or relevant counseling point for short-course antiemetic dexamethasone. Weight loss (option D) — dexamethasone causes weight GAIN (not weight loss) due to increased appetite and fluid retention.
[/expand]Which of the following oral agents requires antiemetic prophylaxis?
A. Capecitabine
B. Letrozole
C. Temozolomide
D. Erlotinib
Explanation: Temozolomide at doses ≥ 75 mg/m²/day is classified as MODERATELY EMETOGENIC — antiemetic prophylaxis is required. Per NCCN guidelines, temozolomide ≥ 75 mg/m²/day should be considered moderately emetogenic with concurrent radiation. This is an important distinction because many assume only IV chemotherapy causes significant CINV. Capecitabine (option A) and erlotinib (option D) have MINIMAL TO LOW emetogenic risk — prophylactic antiemetics are not routinely required. Letrozole (option B) is a hormonal agent with essentially no clinically significant emetogenic risk.
[/expand]JZ is a 55-year-old male with multiple myeloma and osteolytic bone lesions starting on monthly zoledronic acid. Which adverse events would you counsel JZ about?
A. Acute renal failure, osteonecrosis of the jaw, hypocalcemia
B. Atrial fibrillation, acute renal failure, congestive heart failure
C. Osteonecrosis of the jaw, congestive heart failure, bone pain
D. Congestive heart failure, osteonecrosis of the jaw, acute renal failure
Explanation: Zoledronic acid (Zometa) 4 mg IV every 3–4 weeks is approved for bone metastases and multiple myeloma. Key toxicities requiring patient counseling: acute renal failure (nephrotoxic — requires SCr monitoring and dose adjustment), osteonecrosis of the jaw (ONJ — requires baseline dental exam and avoidance of invasive dental procedures), hypocalcemia (calcium and vitamin D supplementation required), and musculoskeletal pain. Congestive heart failure is NOT a typical adverse effect of zoledronic acid — it appears in options B, C, and D as a distractor. Note: Zoledronic acid 5 mg (Reclast) is approved for osteoporosis — different from the 4 mg oncology dose.
[/expand]WW is a 56-year-old male with metastatic colon cancer starting FOLFIRI. On the first night of chemotherapy, he begins experiencing severe abdominal cramping and diarrhea. Which treatment is most appropriate for WW at this time?
A. Octreotide
B. Tincture of opium
C. Loperamide
D. Atropine
Explanation: Irinotecan causes two distinct types of diarrhea — the timing distinguishes them. Acute diarrhea (< 24 hours after irinotecan): occurs immediately after administration; associated with CHOLINERGIC symptoms (abdominal cramping, rhinitis, lacrimation, salivation, diaphoresis); mean duration ~30 minutes. Treatment: ATROPINE is the drug of choice for acute cholinergic irinotecan diarrhea. Delayed diarrhea (> 24 hours after irinotecan): non-cumulative, can be severe; not cholinergic. Treatment: LOPERAMIDE is the drug of choice (high-dose loperamide protocol). WW's diarrhea began on the FIRST NIGHT (acute = cholinergic) → atropine. If it were the next day or later, loperamide would be appropriate. Octreotide is for refractory delayed diarrhea not responding to loperamide.
[/expand]11. KP is a 76-year-old female who is scheduled to receive doxorubicin & cyclophosphamide for her breast cancer. She has significant peripheral neuropathy due to her history of diabetes. In addition, she is from Bosnia and doesn’t speak English very well. What risk factors does KP have for extravasation?
- A. Gender, cyclophosphamide, breast cancer, language barrier (4%)
- B. Gender, doxorubicin, breast cancer, neuropathy (20%)
- C. Age, cyclophosphamide, neuropathy, language barrier (44%)
- D. Age, doxorubicin, neuropathy, language barrier (62%)
- Older age increases the risk of having extravasation, as older patients may have small and/or fragile veins. KPs peripheral neuropathy may prevent her from realizing when the drug is being extravasated. Language barriers may impair optimal communication and delay appropriate care for the patient. Doxorubicin is a known vesicant, and therefore, KP may be at increased risk of toxicity from the extravasation of this agent.
- Sex (gender) and type of cancer (first and second answers) have no impact on the extravasation risk.
- Furthermore, cyclophosphamide (third answer) is not considered a vesicant, although it may be an irritant.
26. A 69-year-old woman with metastatic breast cancer is scheduled to receive paclitaxel and trastuzumab chemotherapy. Is this chemotherapy regimen considered to be high, moderate, low, or minimal risk for causing emesis?
- A. High (>90%) (16%)
- B. Moderate (30–90%) (35%)
- C. Low (10–30%) (45%)
- D. Minimal (<10%) (4%)
- Trastuzumab (Herceptin). like most monoclonal antibodies, is minimally emetogenic.
- The taxanes (e.g., paclitaxel) are also considered low risk.
- Since this patient is over the age of 50, her risk is less than if she was less than 50 years of age.
55. MJ is a 44-year-old breast cancer woman receiving doxorubicin and cyclophosphamide chemotherapy. The oncologist states that the patient is concerned about experiencing nausea and vomiting from chemotherapy. The oncologist writes the following prophylactic antiemetics: palonosetron dexamethasone, and fosaprepitant because he thinks this will provide the best chance of preventing acute nausea and vomiting; what do you think?
- A. Agree, this will provide equal prevention of nausea and vomiting
- B. Agree, but the patient is at risk for more nausea than vomiting
- C. Agree, but the patient is at risk for more vomiting than nausea
- D. Disagree. Fosaprepitant is not needed in this patient
- This patient is at high risk for acute and delayed emesis since she is a breast cancer patient under the age of 50 receiving an anthracycline/cyclophosphamide containing regimen.
- The use of aprepitant (Emend) or fosaprepitant (Emend for Injection) is recommended in this patient.
- Historically, the incidence of nausea and vomiting are not found equally. A trial with an antiemetic regimen similar to MJ resulted in a nausea incidence of approximately 60%. While acute emesis was 20%.
- The patient’s communication should include prevention of emesis is achieved in the vast majority of the patients but nausea control is challenging.