Oncologic Emergencies Prof. Dr. Khaled Abouelkhair, PhD Medical Oncology SCE, Royal College, UK...

Oncologic Emergencies

Prof. Dr. Khaled Abouelkhair, PhDMedical Oncology SCE, Royal College, UK

Ass. Professor of Clinical OncologyMansoura University, Egypt

Oncologic Emergencies

• Hypercalcemia• Hyperuricaemia / TLS

Hypercalcemia• A patient admitted in the medical floor, known

case of lung cancer metastatic to bone, the nurse reporting that the patient is Lethargic, stupor, as well as Fatigue, Dehydration and constipation. ECG was requested which revealed Cardiac bradycardia, and short QT interval

• What would it be?• Metabolic or Neurologic?

The calcium ion plays a critical role in normal cellular function and signaling (neuromuscular signaling, cardiac contractility, hormone secretion, and blood coagulation).

• Feedback mechanisms maintaining extracellular calcium concentrations within a narrow, physiologic range.

• Normal Ca level (8.9 – 10.1 mg/dl).• Corrected Ca mg/dl = (4- albumin in g/dl) x 0.8 + serum Ca.• Commonest Cancer NSCLC, SCLC, Breast, M.M,

RCC, and NHL (T-cell).• Causes of Hypercalcemia:

– Direct bone destruction– Immobilization– Parathormone like hormones– Medications e.g. Thiazides, Antiestrogens, Vit A– Excessive calcium intake, milk alkali syndrome

Management • First be sure it is true hypercalcemia?• The second most important laboratory test in

the diagnostic evaluation is a PTH level.• Serum creatinine should be measured to assess

renal function. Mild Hypercalcemia: asymptomatic patients with

minimally elevated calcium levels (< 12.0 mg/dL) …Encouragement of oral hydration, mobilization, and elimination of drugs that contribute to hypercalcemia are essential. 2-3 L of intravenous fluid may be requiredover the first 24 h

• Moderate Hypercalcemia: 12 -14 mg/dl symptomatic directed therapy.

• Severe Hypercalcemia: ≥ 14 mg/dl. Emergency– Hydration 3-6 L/24h.– Loop diuretics. Furosemide, 20 to 40 mg IV, may

be initiated after volume expansion is achieved, with subsequent doses given when urine output is < 150 to 200 mL/h. Thiazides are contraindicated.

– Bisphosphonates. Onset of action 2-4 days.– Calcitonin. Rapid onset 2-4 Hours, peak effect in

48 hours, short lived effect. Dose 4-8 IU/Kg S.C Q12h. Works through inhibiting the effects of parathyroid hormones.

– Corticosteroids: only in steroid responsive tumors– Phosphate: rarely used for fear of soft tissue

precipitations.– Cyclo - Oxygenase inhibitor: Indomethacin, rarely

used if other drugs fail.– Dialysis: if renal failure is not improving with

hydration and emerging volume overload.

Zoledronic acid• Prevents bone resorption.• Side Effects: Flu like symptoms, Nausea and vomiting

46%, Fatigue 39%, Fever 32%, Diarrhea 24%, Arthralgia/ myalgia 23%, and deterioration of renal function.

• Delayed onset of action 48 – 72h.• 4mg IV infusion over 15 minutes following

rehydration. May repeat after 7 days if not normo-calcemic and can tolerate hydration.

• Remember dose reduction based on creatinine clearance.

REMEMBER• No Diuretics without Hydration in Hypercalcemia.• Always check creatinine clearance and adjust

doses.• Be aware about renal toxicity of Bisphosphnates

and renal doses.• Calcitonin lost its effect after 2-3 days.• Review medications and stop agents, if feasible,

that may cause hypercalcemia and/or renal impairment.

Tumour Lysis Syndrome

• It’s a rapid development of metabolic abnormalities accompanying the release of intracellular contents into the bloodstream due to tumor cells death.

• Rapid release of intracellular contents can happen spontaneously with high tumor burden or from cell lysis due to cytotoxic agents (even steroids!), cytokine or hormonal therapy .

Aetiology: A–Diseases:

a –Leukemia- Acute and CLL

b–Lymphoma- Burkitt’s - T- Cell - Lymphoblastic

c –Solid tumor- Neuroblastoma - SCLC - Breast Cancer

B - Large tumor burden: - Stage IV extensive rapidly dividing tumors

Precipitating Factors:- Spontaneous - Commencing treatment

Co-factors:- Pre-existing renal insufficiency - hyperuricemia

Metabolic Abnormalities:• Tumor cells contain a high concentration of

potassium and phosphate. Their rapid breakdown will release these electrolytes into the blood resulting in:

Hyperkalemia, Hyperuricaemia, Hyperphosphatemia and hypocalcaemia• Soft tissue calcium phosphate deposition and

hypocalcaemia occur as a result of calcium down-regulation secondary to Hyperphosphatemia

• Renal failure is a common complication.

Presentation:• Many are asymptomatic• Symptoms’ severity reflects the underlying

metabolic abnormalities.1- Hyperkalemia: life-threatening, ventricular dysrhythmias, paresthesia and weakness.

2- Hyperuricaemia: may lead to arthralgia and renal colic, urate nephropathy, fatigue, weakness etc… the worst ARF.3- Hypocalcaemia: Neuromuscular instability with muscle cramps, tetany, anxiety, carpopedal spasms, bronchospasm, confusion and convulsions.

ARF in TLS

ManagementPreventionOnce occurred ARF is a major problem with serious consequences. A good physician is not the one who treats it efficiently but the one who can prevent it. Fix conditions that will make effects worse . NSAIDs Get baseline labs: K, Ca, Phos, Uric Acid, LDH, Cr. Preventing renal failure and severe electrolyte imbalances. Increase urine production with proper hydration. Decrease uric acid concentrations using Allopurinol

(Competitive inhibitor of xanthine oxidase) which decrease uric acid synthesis from Purines but limited efficacy.

Alkalinize urine keeping PH above 6.5 as …………

If occurred….• Continue the same measures Plus.• K+..Resoniums, Diuretics, Ca ++……. • Manage ARF…..Dialysis. • Magic Drug RASBURICASE (recombinant urate oxidase)

promotes catabolism of uric acid Allantoins (10x more soluble than uric acid).

What are the differences between Allopurinol and Rasburicase

• Oral versus IV• Prevention and treatment• Nephrotoxic• Needs dose adjustment• Fast action• Drug - drug interactions• Inhibits Enzymatic reactions or an enzyme• Readily revert metabolic abnormaliti es including ARF• Needs alkalinization

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