Chemotherapy and supportive pharmacology — formative SAQs

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]