9.1 Chemotherapy Principles, Classes, and Pediatric Protocols

Chemotherapy remains the backbone of most pediatric cancer protocols. CPHON Domain III.A.1 and III.B.1 cluster hematologic and solid-tumor chemotherapy together: you are tested on cell-cycle logic, class-specific toxicities, and how pediatric protocols actually run—not on reciting a single cooperative-group protocol number as the 2026 standard.

Pediatric regimens are multi-agent, risk-adapted, and almost always include central nervous system (CNS) prophylaxis when the disease can hide in sanctuary sites. Doses are calculated from body surface area (BSA) in most school-age children and from weight in many infant pathways. Independent double-checks exist because one wrong route—especially intrathecal (IT) vincristine—kills.

Cell-cycle phase-specific versus nonspecific

Malignant cells move through G0 (rest), G1 (growth), S (DNA synthesis), G2 (prepare to divide), and M (mitosis). Phase-specific drugs kill cells in one window and are schedule-dependent: a delayed S-phase infusion is not the same treatment as the dose given on time. Phase-nonspecific drugs damage DNA whether the cell is dividing or resting; they are more dose-dependent. Multi-agent pediatric backbones combine both so clones in different phases are hit and so toxicities do not all land on the same organ on the same day.

A 5-year-old on ALL induction is living this table in one week: dexamethasone (mood, gastritis), vincristine (constipation, neuropathy, vesicant, IV only), pegaspargase (pancreas, clot, allergy), and often an anthracycline (heart, vesicant, red urine). The nurse who studies classes as a list but cannot attach a bedside watch will miss the exam item.

Vinca alkaloids — the IT never event

Vincristine is the pediatric workhorse vinca. It causes peripheral neuropathy (foot drop, jaw pain, loss of deep-tendon reflexes), ileus and constipation that can progress to obstruction, and rarely the syndrome of inappropriate antidiuretic hormone secretion (SIADH). It is a vesicant.

The item that must never be missed: vincristine given intrathecally is fatal. Accidental IT vincristine has killed children. Nursing controls are not optional etiquette:

• Two-nurse independent verification of route as well as patient, drug, and dose.
• Never prepare or have vincristine in a syringe at the same time as IT methotrexate is being drawn or carried to the lumbar-puncture tray.
• Many institutions dispense intravenous vincristine in a minibag, not a syringe, so it cannot be injected into a spinal needle.
• IT methotrexate is preservative-free and labeled for IT use; vincristine is never labeled for IT use.

If someone hands you "the IT syringe" and it is vincristine, you stop the procedure. There is no slow-injection recovery.

Antimetabolites

Methotrexate (MTX) is given intravenously (including high-dose), intrathecally, and orally. High-dose MTX is its own nursing protocol: vigorous hydration, urine alkalinization (keep urine pH at or above the protocol threshold, commonly around 7), timed leucovorin rescue, and serial MTX levels. Escalate or extend rescue per protocol if clearance is delayed. Nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, and some penicillins can delay MTX clearance—flag them before the bag is hung. Mucositis and nephrotoxicity are the headline toxicities; hepatotoxicity also occurs.

Mercaptopurine (6-MP) is the daily oral ALL-maintenance agent. Hepatotoxicity and myelosuppression are expected. Thiopurine methyltransferase (TPMT)—and NUDT15 on many contemporary panels—variants increase toxicity; protocol dose reductions follow genotype or unexpected cytopenia. Teach families not to crush or share tablets carelessly.

Cytarabine, especially high-dose, causes chemical conjunctivitis. Start prophylactic steroid eye drops during and after the protocol window. Cerebellar toxicity (nystagmus, ataxia, dysarthria) is a stop-and-notify finding. Nelarabine appears on T-ALL pathways and is famous for neurotoxicity: somnolence, neuropathy, and rare severe ascending weakness. A new inability to walk after nelarabine is not "tired from the hospital."

Anthracyclines, alkylators, platinum, enzymes, steroids, and etoposide

Doxorubicin and daunorubicin are vesicants. Urine and body fluids may turn red-orange; teach that this is expected pigment, not hemorrhage. The organ that limits lifetime therapy is the heart: cumulative lifetime dose is tracked in doxorubicin-equivalents on the treatment summary. Dexrazoxane appears as a cardioprotectant on some pediatric protocols and, separately, as an anthracycline-extravasation antidote concept. Echo surveillance belongs in late-effects teaching.

Cyclophosphamide and ifosfamide generate acrolein, which inflames the bladder. Mesna plus hyperhydration protect against hemorrhagic cystitis. Ifosfamide additionally causes encephalopathy (chloroacetaldehyde) and renal tubular injury. Confusion, somnolence, or new gross hematuria after an ifosfamide day is not "just chemo fatigue."

Cisplatin and carboplatin damage cochlear hair cells and renal tubules. Cisplatin is the classic delayed-nausea, magnesium-wasting, high-frequency hearing-loss drug. Carboplatin is more myelosuppressive and still ototoxic in young children. Serial audiograms are not optional after platinum. Delayed chemotherapy-induced nausea and vomiting (CINV) after cisplatin can last days—antiemetic teaching does not stop when the bag is empty.

Asparaginase and pegaspargase deplete asparagine. Watch hypersensitivity (may require a switch to an Erwinia-derived asparaginase such as crisantaspase), silent inactivation, thrombosis including CNS events, pancreatitis, and hyperglycemia. Abdominal pain after pegaspargase is pancreatitis until lipase says otherwise.

Corticosteroids (prednisone, dexamethasone) cause mood lability, gastritis, hyperglycemia, immunosuppression including Pneumocystis risk on ALL pathways, and avascular necrosis. Dexamethasone has more CNS penetration and a harsher AVN and myopathy profile on many protocols.

Etoposide can drop blood pressure if infused too fast. Slow the rate; do not assume anaphylaxis as the only cause of hypotension. Etoposide also carries a secondary AML risk concept, often KMT2A-rearranged and typically a few years later—teach the concept, not a made-up percentage.

Pediatric protocols and BSA dosing

Children's Oncology Group (COG) and other cooperative-group studies share a design language: multi-agent blocks, risk adaptation from age, white-cell count, genetics, CNS status, and measurable residual disease, and CNS-directed therapy (IT chemotherapy plus high-dose systemic agents with CNS penetration, with radiation reserved for selected high-risk CNS disease). Do not memorize one protocol code as the national 2026 standard; arms change. You will be tested on backbone logic and class toxicities.

BSA dosing (mg/m²) is the default for most cytotoxics in children who are not infants. A commonly used formula is Mosteller: BSA (m²) equals the square root of (height in cm times weight in kg, divided by 3600). Recalculate when weight changes. Infants are often dosed by weight (mg/kg) because BSA-based milligram totals can overdose a small baby; the cutoff may be age, weight, or a BSA threshold and is protocol-specific. Never invent a single infant cutoff as ONCC fact. Two nurses independently recheck height, weight, BSA or kg dose, caps, and the final milligram amount before hanging the bag.

Worked picture: a 6-year-old, 120 cm and 22 kg, has BSA of about 0.86 m² (square root of 2640/3600). Vincristine 1.5 mg/m² is about 1.3 mg, still under typical single-dose caps on many protocols. A 4-month-old at 6 kg is not automatically dosed from an adult-style BSA calculator without the infant rule on that protocol.

The CPHON product is a nurse who can name the class, the organ it injures, the rescue that belongs with it (leucovorin, mesna, steroid drops, dexrazoxane on selected protocols), and the one route that must never be used for vincristine.