Oncologic Emergencies: When Cancer or Its Treatment Turns Acute
Most of oncology is measured in weeks and cycles. But a handful of situations are measured in hours — where the tumour, or the chemotherapy meant to shrink it, suddenly threatens the heart, the kidneys, the spinal cord, or the airway. Recognizing these six emergencies, and reaching for the right drug fast, is often the difference between a full recovery and a catastrophe. This is the pharmacology of the oncology 'crash call'.
A young man with a huge, bulky lymphoma (Lymphoma) receives his very first dose of chemotherapy and, for the first time in weeks, feels the pressure in his belly ease. He looks better. Then, six hours later, he is confused, his heart is racing and skipping, and a monitor shows peaked T-waves. Nothing new has grown — the opposite has happened. The chemotherapy worked TOO well: billions of tumour cells burst at once and emptied their contents — potassium, phosphate, and uric acid — straight into his blood. The treatment succeeding is exactly what nearly kills him. This is tumour lysis syndrome, and a single enzyme drug that dissolves uric acid will pull him back.
Tumour lysis syndrome: when winning floods the blood
The mechanism is pure arithmetic of dying cells. Tumour lysis syndrome (TLS) happens when a large mass of malignant cells dies rapidly — typically hours to days after starting chemotherapy in a bulky, fast-dividing, chemo-sensitive tumour such as acute leukaemia or high-grade lymphoma (occasionally even spontaneously before treatment). As the cells rupture, they dump their intracellular contents into the circulation faster than the kidneys can clear them. The result is a classic quartet: hyperkalaemia (high potassium), hyperphosphataemia (high phosphate), hyperuricaemia (high urate), and — because the released phosphate binds calcium — hypocalcaemia (low calcium). The two lethal edges are cardiac arrhythmia from the potassium, and acute kidney injury (AKI) as urate and calcium-phosphate crystals clog the renal tubules.
Because it is so predictable, TLS is a disease you prevent, not just treat. The first pillar is aggressive intravenous hydration, started BEFORE chemotherapy: flooding the kidneys with fluid dilutes the urate and phosphate and keeps urine flowing to flush out crystals. The second pillar is lowering the urate — and here two very different drugs share the name but not the mechanism.
Allopurinol is a xanthine oxidase inhibitor: it blocks the enzyme that makes uric acid, so it PREVENTS new urate from forming. But it does nothing to the urate already there, and works slowly — good for lower-risk patients as prophylaxis. Rasburicase is recombinant urate oxidase (an enzyme humans lost in evolution): it converts EXISTING uric acid into allantoin, which is far more water-soluble and easily excreted. It drops urate within hours — the drug of choice for high-risk or established TLS. Crucial catch: rasburicase is contraindicated in G6PD deficiency, because the hydrogen peroxide it generates triggers severe haemolysis.
Note what we deliberately DON'T do anymore: routine urine alkalinization. It was once used to keep urate soluble, but it makes calcium-phosphate crystals precipitate MORE readily in the tubules — trading one crystal problem for another. Modern practice relies on hydration plus rasburicase, not bicarbonate. Manage the electrolytes as they come: treat the hyperkalaemia (see the cardiac chapter), bind phosphate, and treat symptomatic hypocalcaemia — but be cautious giving calcium, as it can worsen calcium-phosphate deposition.
- TLS = rapid tumour cell death → high K⁺, high phosphate, high urate, low calcium, AKI.
- Highest risk: bulky, fast-growing, chemo-sensitive tumours (acute leukaemia, high-grade lymphoma).
- Prevent it: aggressive IV hydration started BEFORE chemotherapy.
- Allopurinol PREVENTS new urate (xanthine oxidase inhibitor); rasburicase DESTROYS existing urate fast.
- Rasburicase is contraindicated in G6PD deficiency (haemolysis).
- The killers are hyperkalaemic arrhythmia and crystal-induced acute kidney injury.
Hypercalcaemia of malignancy: the commonest metabolic emergency
It is the metabolic emergency you will meet most often. Hypercalcaemia of malignancy is the most common metabolic emergency in cancer. Most often it is driven by parathyroid hormone-related peptide (PTHrP) secreted by a tumour (classically squamous cell lung cancer), or by extensive bone metastases dissolving bone directly. The calcium climbs, and the symptoms are famously vague — the old mnemonic 'stones, bones, groans and psychic moans': kidney stones, bone pain, abdominal pain and constipation, and confusion or lethargy. High calcium also blocks the kidney's ability to concentrate urine, causing polyuria and, in turn, profound dehydration.
The treatment order matters more than the drug list. The first and most urgent step is aggressive intravenous rehydration with normal saline: these patients are massively volume-depleted, and simply restoring fluid dilutes the calcium and lets the kidneys excrete it. Only after rehydration do we reach for the bone drugs. Bisphosphonates — zoledronic acid is the standard — poison the osteoclasts that are dissolving bone, but they work slowly, taking 2–4 days for full effect. Denosumab, a monoclonal antibody against RANKL, is an alternative that also shuts down osteoclasts and is useful when the kidneys are too poor for bisphosphonates. For a patient who is dangerously high and cannot wait days, calcitonin gives rapid but short-lived control within hours, buying time until the bisphosphonate takes hold.
- Commonest cause: PTHrP secretion (squamous lung cancer) or bone metastases.
- Symptoms: confusion, constipation, polyuria, dehydration ('stones, bones, groans, moans').
- Step 1 is ALWAYS IV fluids (normal saline) — rehydrate before anything else.
- Bisphosphonates (zoledronic acid) or denosumab lower calcium by stopping osteoclasts.
- Calcitonin gives fast but short-lived control while bisphosphonates take effect.
The 'don't-miss' compressions: cord and vena cava
Two emergencies are defined by a tumour pressing on something vital, and both are time-critical. Malignant spinal cord compression is the one you must never miss: a tumour deposit in or around the spine presses on the cord, and the warning sign is new or worsening back pain — often before any weakness — followed by leg weakness, sensory loss, and bladder or bowel dysfunction. Once neurology sets in, the window to preserve walking is measured in hours. The immediate move, before imaging is even complete, is high-dose dexamethasone to reduce the swelling around the cord, followed by an urgent MRI to localize it and then definitive radiotherapy or surgical decompression. Every hour of delay costs neurological function that may never return.
Superior vena cava (SVC) obstruction is the other compression: a mediastinal tumour (often lung cancer or lymphoma) presses on the SVC, blocking the return of blood from the head and arms. The patient develops facial and arm swelling, distended neck and chest veins, and sometimes breathlessness or a plethoric, dusky face made worse by bending forward. Once feared as instantly lethal, it is usually more subacute — but airway or cerebral compromise makes it urgent. Management combines corticosteroids to reduce oedema, endovascular stenting of the SVC to restore flow quickly, and treating the underlying tumour with chemotherapy or radiotherapy.
Dexamethasone is the workhorse steroid across these emergencies — cord compression, SVC obstruction, and raised intracranial pressure from brain metastases — for one reason: it powerfully reduces the vasogenic oedema that tumours provoke around neural tissue, and it has minimal mineralocorticoid (salt-retaining) activity, so it swells the patient far less than hydrocortisone would. In suspected cord compression, giving dexamethasone should NOT wait for the MRI — the imaging confirms and localizes, but the steroid protects the cord in the meantime.
Neutropenic sepsis and the pressured brain
Neutropenic sepsis (febrile neutropenia) is the emergency where chemotherapy has wiped out the neutrophils, leaving the patient defenceless against infection — and a fever may be the ONLY sign, because without neutrophils there is little pus or inflammation to localize it. The rule is unforgiving and famous: broad-spectrum empirical intravenous antibiotics within one hour of presentation, before any culture result returns, because sepsis in a neutropenic patient can become fatal in hours. Do not wait to 'find the source' — treat first. (The antibiotic choice and the full workup belong to the Antimicrobials section and the dedicated febrile-neutropenia chapter.)
Finally, raised intracranial pressure from brain metastases rounds out the list. Secondary tumours in the brain provoke a rim of vasogenic oedema that raises intracranial pressure, producing headache (classically worse in the morning or on coughing), nausea and vomiting, drowsiness, and focal neurological signs or seizures. The immediate pharmacological answer is again dexamethasone, which shrinks the peritumoural oedema and can relieve symptoms strikingly within a day, buying time for definitive radiotherapy, surgery, or stereotactic treatment.
- Cord compression: new back pain → high-dose dexamethasone NOW + urgent MRI + radiotherapy/surgery.
- SVC obstruction: facial/arm swelling, distended veins → steroids, stenting, treat the tumour.
- Neutropenic sepsis: fever may be the only sign → empirical IV antibiotics within ONE hour.
- Raised ICP from brain metastases → dexamethasone to shrink peritumoural oedema.
- Dexamethasone is the shared steroid: strong anti-oedema, minimal salt retention.
- Starting chemotherapy in a bulky, fast-growing tumour without TLS prophylaxis (hydration + allopurinol or rasburicase).
- Giving rasburicase in G6PD deficiency — it triggers severe haemolysis.
- Delaying dexamethasone or the MRI in suspected cord compression — the neurology window is measured in hours.
- Treating hypercalcaemia with a bisphosphonate before rehydrating — fluids must come first.
- Waiting to identify a source before giving antibiotics in neutropenic sepsis — treat within the hour.
A patient with bulky Burkitt lymphoma is due to start chemotherapy. Which intervention BEST prevents the acute kidney injury of tumour lysis syndrome, and what must you check before one specific drug?
- Tumour lysis: rapid cell death → high K⁺/phosphate/urate, low Ca²⁺, AKI. Prevent with hydration + allopurinol (blocks new urate) or rasburicase (destroys existing urate; avoid in G6PD deficiency).
- Hypercalcaemia of malignancy: IV fluids FIRST, then a bisphosphonate (zoledronic acid) or denosumab; calcitonin for rapid short-term control.
- Cord compression and raised ICP from brain metastases → high-dose dexamethasone now; SVC obstruction → steroids + stenting + treat the tumour.
- Neutropenic sepsis: empirical IV antibiotics within one hour — fever may be the only clue.
- DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology — Oncologic emergencies: tumour lysis, hypercalcaemia, cord compression, SVC syndrome.
- Katzung BG. Basic & Clinical Pharmacology — Agents affecting bone mineral homeostasis; uric acid–lowering drugs (allopurinol, rasburicase).
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Corticosteroids; bisphosphonates and denosumab; urate-lowering therapy.
- Cairo MS, Bishop M. Tumour lysis syndrome: classification and consensus grading and management.
- NICE / ESMO clinical guidance — Metastatic spinal cord compression, hypercalcaemia of malignancy, and neutropenic sepsis (empirical antibiotics within one hour).
