Paeds SAQs · clinical-pharmacology-and-therapeutics
Chemotherapy and supportive pharmacology — formative SAQs
Two MedVellum formative short-answer questions on chemotherapy and supportive pharmacology in children: dexrazoxane cardioprotection for the high-cumulative-dose anthracycline child with the vincristine-intravenous-only route rule, and the antiemetic ladder for highly emetogenic regimens with colony-stimulating factor prophylaxis for febrile neutropenia and palifermin for transplant mucositis. The marks and timing support transparent self-assessment. They are not an official board format or pass standard.
On this page & tools
Target exams
SAQ 1 — Dexrazoxane cardioprotection and the vincristine route rule
Question 1 — 10 formative marks; suggested time 15 minutes [1]
An eight-year-old girl receiving doxorubicin for acute lymphoblastic leukaemia has her cumulative anthracycline dose tracked cycle by cycle. The oncology team is considering adding dexrazoxane as the cumulative dose rises. [1]
- Explain the mechanism of anthracycline cardiotoxicity and how dexrazoxane protects the heart, and state the approximate cardioprotection dose ratio. (3 marks)
- State the cumulative anthracycline dose threshold that typically triggers the dexrazoxane decision and the surveillance that supports it. (2 marks)
- A doxorubicin infusion extravasates at the central line. Give the immediate pharmacological management, the time window, and one practice that is contraindicated. (3 marks)
- Separately, vincristine is due on the same list as an intrathecal procedure. State the route rule, the consequence of error, and the prevention system. (2 marks) [7]
Full-credit answer — SAQ 1
Reveal full-credit answer for SAQ 1
1. Mechanism of cardiotoxicity and dexrazoxane protection
The anthracyclines doxorubicin and daunorubicin intercalate DNA and poison topoisomerase, but the cardiotoxicity comes from a second action: the drug binds iron in the cardiomyocyte and the iron catalyses a runaway free-radical cascade that destroys cardiac cells, which regenerate poorly. Dexrazoxane is an intracellular iron chelator: given before the anthracycline it binds the iron before the radical cascade begins, protecting the heart without shielding the leukaemia. The cardioprotection ratio is about ten parts dexrazoxane to one part doxorubicin, given ahead of each anthracycline dose. [1] [2]
2. Threshold and surveillance
The dexrazoxane decision is reserved for the child whose cumulative anthracycline dose crosses into the high-risk territory, classically above about 300 mg per square metre of doxorubicin equivalent. The surveillance that drives the decision is echocardiography and troponin run across the course, because the biomarker follow-up ties the early troponin rise to the later echocardiographic decline, so the surveillance is the signal, not a checkbox. [1] [2]
3. Extravasation management
An anthracycline extravasation is managed with dexrazoxane intravenously within six hours of the spill, daily for three days, body-surface-area banded — the Mouridsen multicentre regimen. Cold compresses are contraindicated for anthracycline extravasation; cold is the management for vinca injury and worsens the anthracycline outcome. Surgical review follows for the necrosis that a delayed rescue allows. [7]
4. Vincristine route rule
Vincristine is given by the intravenous route only, and into the cerebrospinal fluid it is uniformly fatal — the microtubule blockade ascends the neuraxis and the child dies of ascending paralysis and brainstem failure within days. The prevention is a system, not a memory: vincristine is diluted in a minibag rather than a syringe so it cannot be confused with the small-volume intrathecal drugs, intrathecal drugs are prepared and delivered at a separate time, and two clinicians check independently. [7]
SAQ 2 — Antiemetic ladder, febrile neutropenia and mucositis
Question 2 — 10 formative marks; suggested time 15 minutes [3]
A six-year-old boy is to start a cisplatin-containing regimen for a solid tumour. The team is building the supportive pharmacology plan covering nausea, neutropenia and mucositis. [3]
- Describe the antiemetic combination for a highly emetogenic cisplatin regimen, naming the three drug classes, their receptors, and the delayed window to warn the family about. (3 marks)
- State the colony-stimulating factor prophylaxis options (filgrastim and pegfilgrastim) with their doses and schedules, and the risk threshold that justifies primary prophylaxis. (3 marks)
- A child undergoing autologous stem-cell transplant is at high risk of severe oral mucositis. Name the supportive medicine, its mechanism, and its dosing schedule. (2 marks)
- The child presents neutropenic with a fever. Give the immediate management and the antibiotic principle. (2 marks) [5]
Full-credit answer — SAQ 2
Reveal full-credit answer for SAQ 2
1. The antiemetic combination for cisplatin
Cisplatin sits at the top of the emetogenic ladder, so the plan is the triple combination of ondansetron (a 5-HT3 receptor antagonist), aprepitant (an NK1 receptor antagonist that blocks substance P) and dexamethasone (covering the inflammatory arm). The combination covers the acute phase (first twenty-four hours) and the delayed phase (forty-eight to ninety-six hours after the infusion), and the delayed window is the one families must be warned about because the vomiting recurs when they expect it to have settled. Mind dose-related ondansetron QT prolongation at higher intravenous doses. [3] [4]
2. Colony-stimulating factor prophylaxis
Filgrastim is given at about 5 micrograms per kilogram per day subcutaneous, started after the chemotherapy to shorten the neutropenic nadir. Pegfilgrastim, the long-acting form, is given at about 100 micrograms per kilogram subcutaneous as a single dose per cycle because a polyethylene glycol moiety extends its half-life. Primary prophylaxis is justified when the regimen carries a febrile neutropenia risk of about twenty per cent or higher, or when the child carries factors that raise that risk, per the ASCO guideline. Bone pain is expected as the marrow expands. [5]
3. Mucositis prevention
Palifermin is recombinant keratinocyte growth factor that binds receptors on oral epithelium and accelerates the mucosal repair that the cytotoxic has stalled. The schedule is about 60 micrograms per kilogram per day intravenous for six doses — three days before and three days after the stem-cell transplant conditioning — established by the Spielberger trial in the autologous transplant population. [6]
4. The febrile neutropenic child
A neutropenic child with a fever is in medical emergency. I assess for sepsis on the standard paediatric pathway, take blood cultures from every lumen of the central line and a peripheral site, a full blood count with differential and a CRP, and begin empirical broad-spectrum antipseudomonal antibiotics within the hour — not after the cultures grow, but at the moment the fever and neutropenia are confirmed. The antibiotics narrow once the organism and sensitivity return, and the child is admitted. [5]
References
- [1]Lipshultz SE; Rifai N; Dalton VM; Levy DE; Silverman LB; Lipsitz SR The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia The New England journal of medicine, 2004.PMID 15247354
- [2]van Dalen EC; Caron HN; Dickinson HO; Kremer LC Cardioprotective interventions for cancer patients receiving anthracyclines Cochrane database of systematic reviews, 2011.PMID 21678342
- [3]Dupuis LL; Sung L; Molassiotis A; Orsey AD; Tissing W; van de Wetering M 2016 updated MASCC/ESMO consensus recommendations: Prevention of acute chemotherapy-induced nausea and vomiting in children Supportive care in cancer, 2017.PMID 27565788
- [4]Kang HJ; Loftus S; Taylor A; DiCristina C; Green S; Zwaan CM Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial The Lancet. Oncology, 2015.PMID 25770814
- [5]Smith TJ; Khatcheressian J; Lyman GH; Ozer H; Armitage JO; Balducci L 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline Journal of clinical oncology, 2006.PMID 16682719
- [6]Spielberger R; Stiff P; Bensinger W; Gentile T; Weisdorf D; Kewalramani T Palifermin for oral mucositis after intensive therapy for hematologic cancers The New England journal of medicine, 2004.PMID 15602019
- [7]Mouridsen HT; Langer SW; Buter J; Eidtmann H; Rosti G; de Wit M Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies Annals of oncology, 2007.PMID 17185744