Cancer therapy complications and supportive care: Viva

This is a boy on a high emetogenic induction regimen presenting three overlapping toxicities: the breakthrough chemotherapy-induced nausea and vomiting, the severe oral mucositis, and the febrile neutropenia. The structured oral runs from the antiemetic management through the mucositis, the fever and the neutropenia, and it ends with the dexrazoxane cardioprotection that protects the heart across the anthracycline exposure and into the survivorship. [1][9]

Opening: recognise the three toxicities

Examiner. The boy has vomited three times despite the ondansetron, his mouth is ulcerated and he cannot eat, and he has a fever of 38.7 with a neutrophil count of 120. What are the three problems, and why did the vomiting break through? [1]

Candidate. The three problems are the breakthrough chemotherapy-induced nausea and vomiting, the severe oral mucositis of the WHO grade 3 or 4, and the febrile neutropenia. The vomiting broke through because the cyclophosphamide above one gram per square metre is a high emetogenic agent, and the ondansetron alone is underpowered for the risk. The Dupuis guideline of the Pediatric Oncology Group of Ontario sets the standard that the high emetogenic regimen receives the three-drug combination of the 5-HT3 antagonist plus the dexamethasone plus the NK1 antagonist aprepitant, and the single agent fails. [1]

Branch 1: the antiemetic management

Examiner. What is the antiemetic combination, and how is the ondansetron dosed? [1]

Candidate. The three-drug combination is the 5-HT3 antagonist plus the dexamethasone plus the aprepitant. The ondansetron is the 5-HT3 antagonist, given at 0.15 mg per kg per dose to a maximum of 8 mg per dose, and the dexamethasone and the aprepitant are added for the high emetogenic risk. The aprepitant is the NK1 antagonist that blocks the substance P pathway, and it is continued through the days two and three for the delayed nausea. The mediators of the vomiting are the 5-hydroxytryptamine released from the injured gut and the substance P released in the brainstem, and the two receptors, the 5-HT3 and the neurokinin-1, are the targets of the two main classes of the antiemetic. [1]

Examiner (probe). And why does the single agent fail? [1]

Candidate. Because the high emetogenic regimen produces the vomiting through both the 5-hydroxytryptamine and the substance P pathways, and the 5-HT3 antagonist alone blocks only the first. The three-drug combination reduces the acute vomiting to a fraction of what the single agent achieves, and the breakthrough vomiting on the day one predicts the refractory nausea through the whole cycle, so the matched prophylaxis is started before the next dose. [1]

Branch 2: the mucositis and the fever

Examiner. How do you grade and manage the mouth, and how do you respond to the fever and the neutropenia? [9]

Candidate. The extensive ulceration that stops the eating and the drinking is the severe mucositis of the WHO grade 3 or 4. The grade 3 is the ulcers with the liquid diet only, and the grade 4 is the oral intake impossible. The analgesia is escalated to the opioid by the infusion or the patient-controlled analgesia, and the nasogastric or the intravenous nutrition is started because the oral intake is impossible. The single temperature of 38.7 degrees with the absolute neutrophil count of 120 is the febrile neutropenia, because the threshold is the single temperature at or above 38.3 degrees with the count under 500. I take the blood cultures from each lumen of the central line and give the empiric antipseudomonal beta-lactam such as cefepime within one hour, because the delay kills the neutropenic child. [4][9]

Examiner (probe). What prevents the mucositis for the next cycle, and how do you decide the low-risk step-down for the fever? [4]

Candidate. The prevention rests on the MASCC and ISOO evidence. The oral cryotherapy with the ice chips is suggested for the short-half-life mucotoxic chemotherapy, the low-level laser photobiomodulation is recommended for the stem-cell transplant recipients, and the palifermin at 60 microg per kg per day is given before and after the high-dose conditioning. For the fever, the reassessment at the 48 to 72 hours determines the low-risk child, defined by the stable clinical state and the negative cultures, who can be stepped down to the oral ciprofloxacin with the amoxicillin and the clavulanate, following the Freifeld and Pizzo principle of the outpatient management. [4]

Closing: the long-term heart

Examiner. The boy will receive the anthracyclines across the treatment. How do you protect the heart, and what is the evidence? [6]

Candidate. The dexrazoxane is the primary cardioprotection, recommended by the 2022 harmonisation guideline of de Baat and the International Late Effects of Childhood Cancer Guideline Harmonization Group for the child who is expected to receive the anthracycline. It is given at a ten-to-one ratio with the doxorubicin dose, so that 300 mg per square metre of the dexrazoxane accompanies 30 mg per square metre of the doxorubicin, and it chelates the iron and interrupts the free-radical cascade that scars the cardiomyocyte. The Chow study of the childhood cancer survivors, published in the Journal of Clinical Oncology in 2023, confirmed that the dexrazoxane preserves the long-term heart function without compromising the cancer control, addressing the past concern about the efficacy and the secondary malignancy. The surveillance is the second pillar, with the baseline echocardiogram before the first anthracycline and the serial echocardiogram and the troponin through the treatment and into the survivorship, because the anthracycline cardiotoxicity is the toxicity with the longest shadow. [6][9]