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Clinical Hub,UW Health Clinical Tool Search,UW Health Clinical Tool Search,Clinical Practice Guidelines,Oncology

Management of Oncologic Emergencies - Adult/Pediatric - Inpatient

Management of Oncologic Emergencies - Adult/Pediatric - Inpatient - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Oncology


1
Management of Oncologic Emergencies
– Adult/Pediatric – Inpatient
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 3
METHODOLOGY ...................................................................................................................... 4
DEFINITIONS ............................................................................................................................ 4
INTRODUCTION ....................................................................................................................... 6
RECOMMENDATIONS .............................................................................................................. 7
UW HEALTH IMPLEMENTATION ............................................................................................14
APPENDIX A. EVIDENCE GRADING SCHEME(S) .................................................................16
APPENDIX B. SUMMARY OF KEY PRACTICE RECOMMENDATION ...................................17
REFERENCES .........................................................................................................................20
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Contact for Content:
Name: Sara Shull, PharmD, MBA, BCPS – Pharmacy, Drug Policy Program
Phone Number: (608) 262-1817
Email Address: ssmith-shull@uwhealth.org
Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS – Pharmacy, Drug Policy Program
Phone Number: (608) 263-1328
Email Address: ptrapskin@uwhealth.org
Guideline Author(s):
Michael Fallon, PharmD, BCOP – Pharmacy
Jason Jared PharmD, BCOP – Pharmacy
Jennifer Piccolo, PharmD, BCOP – Pharmacy
Catherine Renna, PharmD – Pharmacy
Coordinating Team Members:
Mary Mably, RPh, BCOP – Pharmacy
Review Individuals/Bodies:
Chemotherapy Council Subcommittee
Toby Campbell, MD – Medicine-Hematology/Oncology
Margo Hoover-Regan, MD – Pediatric Hematology/Oncology
Mark Juckett, MD – Medicine-Hematology/Oncology
Kari Wisinski, MD – Medicine-Hematology/Oncology
David Yang, MD – Clinical Lab
Committee Approvals/Dates:
Chemotherapy Council Subcommittee (Initial Review: 04/12/17)
Pharmacy & Therapeutics Committee (Initial Review: 06/15/17)
Release Date: July 2017 | Next Review Date: July 2020
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Executive Summary
Guideline Overview
This clinical practice guideline contains recommendations for the prevention, diagnosis,
management, and treatment of oncologic emergencies including tumor lysis syndrome,
hypercalcemia of malignancy, and spinal cord compression.

Key Practice Recommendations
1. Tumor Lysis Syndrome
1.1 Patient should be evaluated for patient risk factors and stratified into low, intermediate,
or high risk categories
1.2 All patients should receive adequate hydration
1.3 All patients should receive allopurinol
1.4 Administration of rasburicase may be recommended to prevent or treat TLS in high risk
patients
1.5 Uric acid, potassium, phosphate, calcium, serum creatinine, and BUN should be
monitored
2. Hypercalcemia of Malignancy
2.1 Patients should be stratified by severity based on corrected calcium and
symptomatology
2.2 All patients should receive adequate hydration
2.3 Pamidronate or zoledronic acid should be initiated in all symptomatic moderate OR
severe hypercalcemia
2.4 Calcitonin may be considered in patients requiring a rapid decrease in serum calcium
2.5 Denosumab may be considered in patients who are unresponsive to bisphosphonates
2.6 Calcium, phosphate, serum creatinine, and BUN should be monitored
3. Spinal Cord Compression
3.1 Magnetic resonance imaging should be obtained within 24 hours of presentation
3.2 Dexamethasone 10 mg intravenously (IV) followed by 16 mg/day by mouth (PO) or IV in
divided doses should be considered

Companion Documents
1. Intravenous Administration of Formulary Medications – Adult – Inpatient/Ambulatory
2. Intravenous Administration of Formulary Medications – Pediatric/Neonatal –
Inpatient/Ambulatory Clinical Practice Guideline
3. Renal Function-Based Dose Adjustments – Adult – Inpatient/Ambulatory
4. Use of Rasburicase – Adult/Pediatric – Inpatient Clinical Practice Guideline

Scope
Disease/Condition(s): Hyperuricemia or high risk for hyperuricemia associated with solid tumor
malignancy, leukemia, or lymphomas; hypercalcemia associated with solid tumor malignancy,
leukemia, or lymphomas; spinal cord compression or cauda equina syndrome associated with
bone metastases

Clinical Specialty: Adult/Pediatric Hematology, Oncology, Bone Marrow Transplant, General
Medicine, Critical Care

Intended Users: Physicians, Advanced Practice Providers, Pharmacists, Nurses, Technical
Support

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Objective(s): The objective of this guideline is to guide the management of oncologic
emergencies including tumor lysis syndrome, hypercalcemia of malignancy, and spinal cord
compression to facilitate prompt and appropriate evidence-based interventions while minimizing
treatment variability

Target Population: Adult and pediatric patients at high risk for tumor lysis syndrome or those
patients experiencing tumor lysis syndrome, hypercalcemia, or spinal cord compression

Interventions and Practices Considered: Supportive care, treatment, prevention, laboratory
monitoring.

Major Outcomes Considered:
1. Hospital length of stay
2. Morbidity/Mortality
3. Appropriate uric acid laboratory test
4. Time to intravenous fluid and medication administration
5. Hospital costs of rasburicase and intravenous allopurinol

Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (e.g., PUBMED) were conducted by the guideline author(s) and
workgroup members to collect evidence for review. Expert opinion and clinical experience were
also considered during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external
organizations and/or arrived at a consensus through discussion of the literature and expert
experience. All recommendations endorsed or developed by the guideline workgroup were
reviewed and approved by other stakeholders or committees (as appropriate).

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Recommendations developed by external organizations maintained the evidence grade
assigned within the original source document and were adopted for use at UW Health.

Internally developed recommendations, or those adopted from external sources without an
assigned evidence grade, were evaluated by the guideline workgroup using an algorithm
adapted from the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) methodology (see Figure 1 in Appendix A).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix A for the rating scheme(s) used within this document.

Recognition of Potential Health Care Disparities:
Health care disparities exist in cancer care. For example, state of the art diagnostic and
therapeutic measures and the opportunity to participate in cancer clinical trials may be less
available in institutions most likely to serve minorities. Additional factors that may influence
outcomes include distrust of the health care system, stigmas related to cancer and death,
literacy and language barriers, and poor expectations regarding the outcome from cancer care.1
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Careful consideration of these disparities should be addressed to ensure the best oncologic
emergent outcome for patients.
Definitions
Tumor Lysis Syndrome (TLS)
1. Patient stratification by risk2
1.1 Patients at low risk for TLS
1.1.1 Indolent Non Hodgkin Lymphoma or other slowly proliferating malignancies and
do not possess characteristics of intermediate- or high-risk patients below
1.2 Patient at intermediate risk for TLS
1.2.1 Diffuse large B-cell lymphoma or other rapidly proliferating malignancies and do
not possess characteristics of high-risk patients below
1.3 Patient at high risk for TLS
1.3.1 High tumor burden as indicated by
1.3.1.1 Bulky disease (>10 cm) OR
1.3.1.2 Elevated lactate dehydrogenase (LDH >2x upper limit of normal) OR
1.3.1.3 Elevated white blood cell count (WBC >100,000 /µL)
1.3.2 Hyperuricemia ≥8 mg/dL
1.3.3 Malignancy
1.3.3.1 Acute myeloid leukemia (AML)
1.3.3.1.1 WBC ≥ 50,000 /µL OR
1.3.3.1.2 Monoblastic AML or uric acid level ≥8 mg/dL
1.3.3.2 Burkitt’s lymphoma
1.3.3.3 Lymphoblastic lymphoma
1.3.3.4 Burkitt’s acute lymphoblastic leukemia
1.3.3.5 Acute lymphoblastic leukemia with a WBC ≥ 100,000 /µL
1.3.4 Host-related factors causing increased risk of TLS
1.3.4.1 Dehydration
1.3.4.2 Preexisting hyperuricemia
1.3.4.3 Decreased urinary flow
1.3.4.4 Preexisting renal dysfunction
1.3.4.5 Acidic urine
2. Diagnostic criteria for TLS (Cairo-Bishop definition)2
1.1 TLS should have 2 or more laboratory changes within 3 days before or 7 days after
cytotoxic therapy
1.1.1 Uric acid ≥ 8 mg/dL OR 25% increase from baseline
1.1.2 Potassium ≥ 6 mg/L OR 25% increase from baseline
1.1.3 Phosphate
1.1.3.1 ≥ 6.5 mg/dL in pediatrics OR 25% increase from baseline
1.1.3.2 ≥ 4.45 mg/dL in adults OR 25% increase from baseline
1.1.4 Calcium ≤ 7 mg/dL or 25% decrease from baseline
3. Clinical criteria for TLS (Cairo-Bishop definition)2
3.1 TLS should have 1 or more clinical complications
3.1.1 Renal insufficiency defined as a serum creatinine >1.5 x ULN
3.1.2 Cardiac arrhythmias
3.1.3 Seizures
Hypercalcemia of malignancy (HCM)
1. Corrected calcium = [0.8 x (4.0-serum albumin)] + serum calcium level
2. Patient stratification by severity3
2.1 Mild hypercalcemia
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2.1.1 Corrected calcium <12 mg/dL AND
2.1.2 Asymptomatic or nonspecific symptoms such as constipation, fatigue, and
depression
2.2 Moderate hypercalcemia
2.2.1 Corrected calcium 12-13.5 mg/dL AND
2.2.2 Asymptomatic (or nonspecific symptoms) or mildly symptomatic with polyuria,
polydipsia, dehydration, anorexia, nausea, muscle weakness, OR changes in
mental status
2.3 Severe hypercalcemia
2.3.1 Corrected calcium >13.5 mg/dL OR
2.3.2 Progression of the symptoms described above including mental status
changes OR renal dysfunction
Spinal Cord Compression (SCC)/Cauda Equina Syndrome
1. Spinal cord compression - compression of the dural sac and its contents by an
extradural tumor mass4
1.1 Minimum radiological evidence for cord compression is indentation of the theca at a
level corresponding to the level of clinical features
1.2 Clinical features include any or all of the following:
1.2.1 Pain (local or radicular)
1.2.2 Weakness
1.2.3 Sensory disturbance
1.2.4 Evidence of sphincter dysfunction
2. Subclinical cord compression – presence of radiographic features in the absence of
clinical features4
3. Patients at high risk for SCC5
3.1 Inability to walk
3.2 Increased deep tendon reflexes
3.3 Compression fractures on radiographs of spine
3.4 Bone metastases diagnosed more than one year earlier
3.5 Age less than 60 years
4. Terms regarding motor function6
4.1 Ambulatory – patients who are able to walk with or without assistance and who may
be mildly paraparetic
4.2 Paretic – patients who are non-ambulatory and paraparetic
4.3 Paraplegic – patients who have only a flicker of or no muscle movement
5. Lower extremity functional scales should be used in infants who have not walked yet
Introduction
Tumor lysis syndrome can occur as a result of spontaneous massive tumor cell lysis or after the
initiation of cytotoxic medications in patients with solid tumor and hematologic malignancies.
Consequently, intracellular contents, including potassium, phosphate, and nucleic acids
subsequently metabolized into uric acid, are released from the cell and enter systemic
circulation.2 Current recommendations for the management of TLS include aggressive hydration
and allopurinol. A limitation of allopurinol is that it only prevents new formation of uric acid and
does not help eliminate uric acid that is already present. Rasburicase, a recombinant urate
oxidase enzyme, metabolizes uric acid into allantoin and is indicated for the treatment and
prevention of hyperuricemia in adult and pediatric patients.7

Hypercalcemia of malignancy occurs via the activation of osteoclasts to accelerate bone-
resorption. In malignancy, osteoclasts are primarily over-stimulated by three mechanisms:
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osteolytic release of cytokines, tumor secretion of parathyroid hormone-related protein (PTHrP),
and tumor production of 1,25-dihydroxyvitamin D (calcitriol).8 Hypercalcemia can lead to
osteoporosis, renal insufficiency, coma, and death and often indicates a poor prognosis for
patients with cancer.8 Current recommendations for the management of hypercalcemia of
malignancy include aggressive hydration and bisphosphonate therapy.

Spinal cord compression occurs when the tumor compresses the spinal cord by invading the
epidural space and results in an inflammatory response and potentially irreversible loss of
neurological function. Clinical manifestations of SCC include pain, motor defects and sensory
deficits which can lead to weakness and paralysis.4 Treatment is directed towards pain control,
minimizing complications and preserving neurological function. Initiation of radiation therapy and
corticosteroids in patients presenting with SCC has been shown to delay the progression of
neurological deficits and, potentially, reverse them in some cases.4
Recommendations
Tumor Lysis Syndrome
1. Patient should be evaluated for patient risk factors and stratified into low, intermediate, or
high risk categories2,9,10 (UW Health high quality evidence, strong recommendation)
1.1 Patients at low to intermediate risk for TLS should receive appropriate care to prevent
TLS
1.2 Patients at high risk for TLS should receive appropriate supportive care to prevent TLS
1.2.1 Rasburicase may be necessary for patient’s at high risk for TLS or for the
management of hyperuricemia
2. Patients at low to intermediate risk for TLS should receive appropriate supportive care2 (UW
Health high quality evidence, strong recommendation)
2.1 Hydration
2.1.1 Adult patients
2.1.1.1 It is recommended to remove potassium, phosphate, and calcium from all IV
fluids2 (UW Health low quality evidence, strong recommendation)
2.1.1.2 Sodium chloride 0.9% IV at a rate of 2-3 L/m2/day to maintain urine output at
80-100 mL/m2/hr is recommended2,9 (UW Health high quality evidence,
strong recommendation)
2.1.1.3 Loop diuretics may be considered in euvolemic or hypervolemic patients to
maintain adequate urine output2 (UW Health high quality evidence, weak
recommendation)
2.1.2 Pediatric patients
2.1.2.1 It is recommended to remove potassium, phosphate, and calcium from all IV
fluids2 (UW Health low quality evidence, strong recommendation)
2.1.2.2 Dextrose 5%-sodium chloride 0.2-0.45% IV at a rate of 1.5-2 times
maintenance requirements to maintain a urine output ≥2 mL/kg/hr is
recommended2 (See Table 1) (UW Health low quality evidence, strong
recommendation)
2.1.3 Comorbidities should be taken into consideration when initiating aggressive fluid
hydration (e.g. renal failure, congestive heart failure, severe anemia)2 (UW
Health low quality evidence, strong recommendation)
Table 1. Maintenance fluid requirements for pediatric patients11
Weight
(kg)
Maintenance fluid per 24 hours Maintenance fluid per hour
0-10 100 mL/kg 4 mL/kg/hr
10-20 1000 mL PLUS 40 mL/hr PLUS
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50 mL/kg for each kg >10 kg 2 mL/kg/hr for each kg >10 kg
≥20 1500 mL PLUS
20 mL/kg for each kg > 20 kg
60 mL/hr PLUS
1 mL/kg/hr for each kg >20 kg

2.2 Allopurinol
2.2.1 Treatment with allopurinol should be initiated in patients 12-48 hours before the
initiation of cytotoxic agents2 (UW Health high quality evidence, strong
recommendation)
2.2.2 Treatment with allopurinol may be continued for up to 3-7 days after induction of
chemotherapy, based on the ongoing risk of TLS development2 (UW Health
moderate quality evidence, weak recommendation)
2.2.3 In adult patients, allopurinol 300 mg PO daily is recommended2,9 (UW Health high
quality evidence, strong recommendation)
2.2.4 In pediatric patients at intermediate risk for TLS, allopurinol 10 mg/kg/day PO in
divided doses is recommended12 2,9,12 (UW Health low quality evidence, strong
recommendation)
2.2.5 In pediatric patients at low risk for TLS, observation may be considered2 (UW
Health moderate quality evidence, weak recommendation)
2.2.6 Allopurinol should be adjusted for renal dysfunction2 (UW Health high quality
evidence, strong recommendation)
2.2.7 Allopurinol doses greater than 300 mg should be given in divided doses2 (UW
Health High quality evidence, strong recommendation)
2.2.8 Dose reductions of 50-70% of 6-mercaptopurine and azathioprine are
recommended when administered concomitantly with allopurinol13 (UW Health
high quality evidence, strong recommendation)
3. Rasburicase is indicated for the prevention of TLS in high risk patients AND treatment of
hyperuricemia secondary to malignancy (uric acid ≥8 mg/dL)
3.1 Appropriate hydration and allopurinol should be optimized to prevent TLS2,9,11-13 (See
Recommendation 2. Patients at low to intermediate risk for TLS) (UW Health high quality
evidence, strong recommendation)
3.2 Rasburicase indications
3.2.1 Administration of rasburicase may be recommended for the prevention of TLS in
high risk patients and management of hyperuricemia (uric acid ≥8 mg/dL) 2,7 (UW
Health Moderate quality evidence, strong recommendation
3.2.2 Rasburicase is contraindicated in patients with a history of glucose-6-phophate
dehydrogenase deficiency. Allopurinol should be utilized in this patient
population7,14 (UW Health high quality evidence, strong recommendation)
3.2.3 Rasburicase is contraindicated in pregnant or lactating females7 (UW Health low
quality evidence, strong recommendation)
3.3 Rasburicase dose
3.3.1 Single dose rasburicase is recommended for prevention of TLS in high risk
patients and treatment of hyperuricemia (uric acid ≥8 mg/dL)15 (UW Health high
quality evidence, strong recommendation)
3.3.1.1 Rasburicase 0.15 mg/kg IV up to a maximum dose of 3 mg for uric acid levels
≤12 mg/dL2,16-18 (UW Health high quality evidence, strong recommendation)
3.3.1.2 Rasburicase 0.15 mg/kg IV up to a maximum dose of 6 mg for uric acid levels
>12 mg/dL may be considered16,17,19 (UW Health moderate quality evidence,
strong recommendation)
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3.3.1.3 Ideal body weight or adjusted body weight for patients who are more than
30% above their ideal body weight, should be used to dose rasburicase18,20
(UW Health moderate quality evidence, strong recommendation)
3.3.1.4 Rasburicase 1.5-3 mg may be considered for prevention of TLS in high risk
patients20 (UW Health low quality evidence, weak recommendation)
3.3.2 For rasburicase doses ≥1.5 mg, rasburicase dose should be rounded to nearest
multiple of 1.5 mg vial7 (UW Health low quality evidence, strong
recommendation)
3.4 Rasburicase administration
3.4.1 Infusion should be run over 30 minutes2,7 (UW Health high quality evidence,
strong recommendation)
3.4.2 For prevention of TLS in high risk patients, rasburicase should be administered
prior to initiation of cytotoxic agents, preferably 4-6 hours prior as uric acid levels
decrease within 4 hours of initial administration7 (UW Health high quality
evidence, strong recommendation)
3.5 Repeat administration of rasburicase
3.5.1 Second dose of rasburicase is indicated if it is >24-48 hours after initial
rasburicase dose AND uric acid level is increasing OR uric acid is ≥ 8 mg/dL16,19
(UW Health moderate quality evidence, strong recommendation)
3.5.2 Rasburicase 0.15 mg/kg IV up to a maximum dose of 1.5-6 mg may be
considered16,17,19,21 (UW Health moderate quality evidence, strong
recommendation)
3.5.3 There is limited clinical evidence to support administration of additional doses of
rasburicase beyond the second dose; further administration is not
recommended22 (UW Health Low quality evidence, weak recommendation)
3.6 Management of electrolyte abnormalities
3.6.1 Hyperphosphatemia
3.6.1.1 For management of asymptomatic hyperphosphatemia, it is reasonable to
maintain adequate hydration and administer phosphate binders, such as
calcium carbonate or sevelamer23 (UW Health very low quality, weak
recommendation)
3.6.2 Hyperkalemia
3.6.2.1 For management of asymptomatic hyperkalemia, sodium polystyrene
sulfonate 1 g/kg PO up to a maximum dose of 15 g may be considered9 (UW
Health very low quality, weak recommendation)
3.6.2.2 For management of severe or symptomatic hyperkalemia, a regimen of
insulin and dextrose can be considered9 (UW Health low quality, strong
recommendation)
3.6.2.3 Renal replacement therapy may be considered in symptomatic or severe
hyperkalemia and hyperphosphatemia22 (UW Health low quality evidence,
strong recommendation)
3.6.3 Hypocalcemia
3.6.3.1 For management of symptomatic hypocalcemia, calcium gluconate 50-100
mg/kg IV up to a a maximum dose of 2 g may be considered2,9 (UW Health
low quality, weak recommendation)
3.7 Urine alkalinization is generally not recommended and should be avoided in patients
with high urine pH and elevated phosphate levels2 (UW Health very low quality evidence,
weak recommendation)
3.7.1 Sodium bicarbonate may be considered for patients with metabolic acidosis2 (UW
Health very low quality evidence, weak recommendation)
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3.7.2 Alkalinization is not required in patients receiving rasburicase2 (UW Health low
quality evidence, strong recommendation)
3.8 Monitoring
3.8.1 Uric acid
3.8.1.1 Uric acid should be monitored every 8-12 hours until stable then every 12-24
hours7 (UW Health high quality evidence, strong recommendation)
3.8.1.2 Uric Acid for Patients on Rasburicase (special laboratory test) should be
ordered post rasburicase administration for 72 hours7 (UW Health high quality
evidence, strong recommendation)
3.8.2 Electrolytes
3.8.2.1 Serum potassium, calcium, phosphate every 8-12 hours until stable then
every 12-24 hours7 (UW Health high quality evidence, strong
recommendation)
3.8.3 Renal function
3.8.3.1 BUN and serum creatinine every 8-12 hours until stable then every 12-24
hours7 (UW Health high quality evidence, strong recommendation)
3.9 HealthLink ordering restriction
3.9.1 Rasburicase may only be ordered by an attending physician or fellow on the
adult OR pediatric, hematology, oncology, bone marrow transplant OR critical
care services
Hypercalcemia of Malignancy
1. Patients should be stratified by severity based on corrected calcium and symptomatology3
(UW Health Low quality evidence, strong recommendation)
1.1 Patients with mild OR asymptomatic moderate hypercalcemia should receive
appropriate supportive care
1.2 Patients with symptomatic moderate OR severe hypercalcemia should receive
appropriate supportive care AND bisphosphonates or other antihypercalcemic
medications
2. Patients with mild OR asymptomatic moderate hypercalcemia should receive appropriate
supportive care
2.1 Remove calcium-containing exogenous sources
2.1.1 Remove calcium from all IV fluids and parenteral and enteral feeding solutions3
(UW Health low quality evidence, strong recommendation)
2.1.2 Discontinue oral calcium supplements3 (UW Health low quality evidence, strong
recommendation)
2.2 Discontinuation of medications that may independently increase calcium levels including
thiazide diuretics, lithium, calcitriol, vitamin D may be considered3 (UW Health low quality
evidence, weak recommendation)
2.3 Diet consisting of <1000 mg of calcium per day may be considered3 (UW Health low
quality evidence, weak recommendation)
2.4 Phosphate supplementation
2.4.1 Phosphate should be replaced orally or administered through a nasogastric tube
as neutral phosphate24 (UW Health low quality evidence, strong
recommendation)
2.4.2 Maintain the calcium-phosphate product <40 mg/dL25 (UW Health moderate
quality evidence, strong recommendation)
2.5 Hydration
2.5.1 Adult patients
2.5.1.1 Sodium chloride 0.9% IV at a rate of 200-500 mL/hr to maintain urine
output at 100-150 mL/hr for 1-3 days is recommended3,26 (UW Health low
quality evidence, strong recommendation)
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2.5.1.2 Loop diuretics may be considered in euvolemic or hypervolemic patients
to maintain adequate urine output3 (UW Health high quality evidence,
weak recommendation)
2.5.1.2.1 Furosemide 20-40 mg IV may be considered to maintain urine
output3 (UW Health moderate quality evidence, weak
recommendation)
2.5.1.2.2 Use contraindicated in patients with hypovolemia or
obstructive renal failure and is not routinely recommended3
(UW Health moderate quality evidence, conditional
recommendation)
2.5.2 Pediatric patients
2.5.2.1 Dextrose 5%-sodium chloride 0.2-0.45% IV at a rate of 1.5-2 times
maintenance requirements to maintain a urine output ≥2 mL/kg/hr is
recommended11 (See Table 1) (UW Health low quality evidence, strong
recommendation)
2.6 Therapies for the treatment of the malignancy should be pursued3,26,27 (UW Health low
quality evidence, strong recommendation)
3. Bisphosphonates and other antihypercalcemic medications are indicated for management of
symptomatic moderate OR severe hypercalcemia
3.1 Appropriate hydration and supportive care should be optimized3,11,24-26 (See
Recommendation 2. Patients with mild OR asymptomatic moderate) (UW Health high
quality evidence, strong recommendation)
3.2 Bisphosphonate therapy
3.2.1 Pamidronate or zoledronic acid should be initiated in all symptomatic moderate
OR severe hypercalcemia3,26 (UW Health high quality evidence, strong
recommendation)
3.2.1.1 Zoledronic acid may be preferred over pamidronate; however, the
differences are of arguable clinical importance28 (UW Health moderate
quality evidence, weak recommendation)
3.2.2 Patients should receive adequate hydration prior to bisphosphonate
administration29,30 (UW Health high quality evidence, strong recommendation)
3.2.2.1 A minimum of 4 hours of hydration or adequate urine output is
reasonable3,26,29,30 (UW Health low quality evidence, strong
recommendation)
3.2.3 Pamidronate
3.2.3.1 Adult patients
3.2.3.1.1 For symptomatic moderate hypercalcemia (12-13.5 mg/dL),
pamidronate 60 mg or 90 mg IV should be administered30 (UW
Health moderate quality evidence, strong recommendation)
3.2.3.1.2 For severe hypercalcemia (>13.5 mg/dL), pamidronate 90 mg
IV should be administered30 (UW Health moderate quality
evidence, strong recommendation)
3.2.3.2 Pediatric patients
3.2.3.2.1 For symptomatic moderate OR severe hypercalcemia
pamidronate 0.5 to 1 mg/kg IV up to a maximum of 90 mg may
be considered31-34 (UW Health low quality evidence, strong
recommendation)
3.2.3.3 Pamidronate should be administered over at least 2 hours30,35,36 (UW
Health moderate quality evidence, strong recommendation)
3.2.3.4 Longer infusions (>2 hours) may be considered in impaired renal
function30,37 (UW Health low quality evidence, strong recommendation)
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3.2.3.5 Pamidronate may be considered in a patient undergoing hemodialysis if a
patient remains symptomatically hypercalcemic despite rehydration,
increased dialysis, and withdrawal of hypercalcemia drugs38 (UW Health
low quality evidence, weak recommendation)
3.2.4 Zoledronic acid
3.2.4.1 For symptomatic moderate OR severe hypercalcemia, zoledronic acid 4
mg IV should be administered29,39 (UW Health moderate quality evidence,
strong recommendation)
3.2.4.2 Dose reduction of zoledronic acid is not recommended for patients with
serum creatinine <4.5 mg/dL29,36 (UW Health moderate quality evidence,
strong recommendation)
3.2.4.3 Zoledronic acid should be administered over at least 15 minutes29,39 (UW
Health moderate quality evidence, strong recommendation)
3.2.4.4 Administration of zoledronic acid over 30-60 minutes may be considered
in impaired renal function40 (UW Health very low quality evidence, weak
recommendation)
3.2.4.5 Benefit versus risk should be evaluated in severe renal impairment
(serum creatinine >4.5 mg/dL)28,29 (UW Health moderate quality evidence,
weak recommendation)
3.2.5 It is reasonable to expect a decrease in serum calcium in 2-4 days and a nadir in
serum calcium in 4-7 days after therapy is initiated37 (UW Health moderate
quality evidence, strong recommendation)
3.2.6 A second dose of pamidronate or zoledronic acid may be considered for patients
who do not achieve goal serum calcium in 7 days3 (UW Health low quality
evidence, weak recommendation)
3.3 Second line therapies
3.3.1 Calcitonin may be considered in patients with severe and life-threatening
hypercalcemia in combination with bisphosphonate therapy27,41 (UW Health low
quality evidence, strong recommendation)
3.3.1.1 Calcitonin dose of 4 units/kg intramuscular (IM) or subcutaneously (SC)
every 12 hours should be considered41,42 (UW Health low quality
evidence, strong recommendation)
3.3.1.2 Dose may be increased to 8 units/kg IM or SC every 12 hours to a
maximum of every 6 hours27,42,43 (UW Health low quality evidence, strong
recommendation)
3.3.1.3 Use of calcitonin for longer than 48 hours is not recommended43,44 (UW
Health low quality evidence, strong recommendation)
3.3.1.4 It is reasonable to expect a decrease in serum calcium within 2-6 hours
and a maximum effect in 24-48 hours44 (UW Health low quality evidence,
strong recommendation)
3.3.1.5 Nasal calcitonin is not recommended for treatment of hypercalcemia45
(UW Health low quality evidence, strong recommendation)
3.3.2 Denosumab may be considered in patients with persistent hypercalcemia after 2
bisphosphonate doses at least 7 days apart AND at least 7 days after second
bisphosphonate dose 46,47 (UW Health low quality evidence, strong
recommendation)
3.3.2.1 Denosumab dose of 60 mg or 120 mg SC is recommended48 (UW Health
moderate quality evidence, strong recommendation)
3.3.2.2 For patients with creatinine clearance <30 mL/min, it may be reasonable
to use a weight-based dosing regimen of 0.3 mg/kg49 (UW Health low
quality evidence, weak recommendation)
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3.3.2.3 Patients with creatinine clearance <30 mL/min should be monitored due
to increased risk of hypocalcemia49,50 (UW Health moderate quality
evidence, weak recommendation)
3.3.2.4 It is reasonable to expect an initial decrease in serum calcium 2-4 days,
with a median response of 9 days, and a complete response 23 days
after therapy is initiated51,52 (UW Health moderate quality evidence, strong
recommendation)
3.3.2.5 A second dose of denosumab may be considered for patients who do not
achieve goal serum calcium in 7 days49 (UW Health low quality evidence,
weak recommendation)
3.3.3 Dialysis may be considered in patients with severe hypercalcemia and renal
insufficiency or heart failure where hydration cannot be safely administered53
(UW Health low quality evidence, weak recommendation)
3.4 Monitoring
3.4.1 Electrolytes
3.4.1.1 Calcium should be monitored every 12-24 hours24 until stable (UW Health
High quality evidence, strong recommendation)
3.4.1.2 Phosphate and magnesium should be monitored every 24 hours34 (UW
Health high quality evidence, strong recommendation)
3.4.2 Renal function
3.4.2.1 BUN and serum creatinine should be monitored at baseline and every 12-
24 hours until stable34 (UW Health high quality evidence, strong
recommendation)
3.5 HealthLink ordering restrictions
3.5.1 Denosumab is restricted to outpatient clinic use
Spinal Cord Compression/Cauda Equina Syndrome
1. Identification of SCC
1.1 Radiographic evidence and clinical features should be evaluated to classify patients as
clinical or subclinical cord compression4 (UW Health high quality, strong
recommendation)
1.2 SCC should be considered in high risk patients with symptoms suggestive of spinal
metastases5 (UW Health moderate quality evidence, strong recommendation)
1.3 Other causes of presentation should be ruled out4 (UW Health low quality evidence,
strong recommendation)
2. Imaging
2.1 Magnetic resonance imaging (MRI) of the whole spine in patients with suspected SCC
should be performed4,54 (UW Health moderate quality evidence, strong recommendation)
2.2 MRI should be done within 24 hours in patients with suspected SCC55 (UW Health
moderate quality evidence, strong recommendation)
2.3 Targeted computed tomography to assess spinal stability and planned verbroplasty,
kyphoplasty, or spinal surgery may be considered4 (UW Health low quality evidence,
strong recommendation)
2.4 Routine imaging of the spine in asymptomatic patients is not recommended56 (UW
Health low quality evidence, weak recommendation)
3. Pharmacological management
3.1 Steroids
3.1.1 Dexamethasone 10 mg IV followed by 16 mg/day PO or IV divided in 2-4 doses
may be considered4,57,58 (UW Health moderate quality evidence, weak
recommendation)
3.1.2 Dexamethasone doses should be tapered over 2 weeks4,58 (UW Health low
quality evidence, weak recommendation)
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3.1.3 Dexamethasone should be transitioned to PO as soon as tolerated58 (UW Health
moderate quality evidence, strong recommendation)
3.1.4 Initiation of dexamethasone should NOT be delayed until radiographic
confirmation4,58 (UW Health moderate quality evidence, strong recommendation)
3.1.4.1 In pediatric patients with suspected hematologic or lymphoid malignancies,
an attempt to obtain diagnostic tissues prior to giving steroids may be
considered (UW Health very low quality evidence, weak recommendation)
3.2 Analgesia
3.2.1 Non-opiate and opiate medications should be considered in combination for
analgesia56 (UW Health moderate quality evidence, strong recommendation)
3.3 Nonpharmalogical management
3.3.1 Risks and benefits of surgical versus medical management (expedited initiation
of chemotherapy) should be considered by the hematologist/oncologist and
neurosurgeon collaboratively in patients with spinal cord compression
3.3.2 Surgical intervention
3.3.2.1 Surgery should be considered in spinal instability59,60 (UW Health low quality
evidence, strong recommendation)
3.3.2.2 Surgery may be considered in patients with neurologic progression during or
after radiation therapy4 (UW Health low quality evidence, weak
recommendation)
3.3.2.3 Surgery may be considered in patients with radioresistant tumors61,62 (UW
Health low quality evidence, weak recommendation)
3.3.3 Radiation therapy
3.3.3.1 For patients with clinical cord compression but without body compression or
spinal instability, XRT should be considered in ambulatory, ambulatory with
assist, paraparetic, and paraplegic patients4,59 (UW Health moderate
evidence, strong recommendation)
3.3.3.2 XRT for recurrent SCC in an area previously irradiated may be considered4
(UW Health low quality evidence, conditional recommendation)
3.3.3.3 XRT monotherapy (e.g. without dexamethasone) may be considered for
patients with no neurological deficits63 (UW Health low quality evidence, weak
recommendation)
3.3.3.4 The role of radiation therapy in the management of pediatric patients with
spinal cord compression due to an initial diagnosis of malignancy is limited
due to late effects of radiation64 (UW Health low quality evidence, weak
recommendation)
Summary of Recommendations
See Appendix B for summary of practice recommendations and doses of commonly used
medications
UW Health Implementation
Potential Benefits:
ξ Minimization in treatment variability of oncologic emergencies
ξ Decreased time to appropriate medication administration
ξ Decreased hospital length of stay

Potential Harms:
ξ Higher risk patients may require initial doses of rasburicase greater than 3 mg to exhibit
a full response
ξ Bisphosphonates are potentially nephrotoxic
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ξ High dose dexamethasone can increase risk of infection especially in
immunocompromised patients

Pertinent UW Health Policies & Procedures
1. UWHC 15.2: Medication Use in Outpatient Care Areas
2. UWHC 8.89: Preventing Non-therapeutic Exposure to Hazardous Drugs
3. UWMF 102.083: Reclast-Zoledronic Acid

Patient Resources
ξ None identified

Guideline Metrics
ξ Adverse reaction drug reporting

Implementation Plan/Clinical Tools
1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines.
2. Release of the guideline will be advertised in the Physician/APP Briefing newsletter.
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the
guideline recommendations (such as the following) will be reviewed for consistency and
modified as appropriate.

Order Sets & Smart Sets
IP – Tumor Lysis – Pediatric – Supplemental [4705]
IP – Spinal Cord Compression – Adult – Admission [1261]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and
treatment of patients. This guideline outlines the preferred approach for most patients. It is not
intended to replace a clinician’s judgment or to establish a protocol for all patients. It is
understood that some patients will not fit the clinical condition contemplated by a guideline and
that a guideline will rarely establish the only appropriate approach to a problem.

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Appendix A. Evidence Grading Scheme(s)

Figure 1. GRADE Methodology adapted by UW Health


GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.






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Appendix B. Summary of Key Practice Recommendation
Figure 2. Prevention and Management of Tumor Lysis Syndrome


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Figure 3. Treatment of Hypercalcemia of Malignancy


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Table 2. Recommended Dose of Common Medications
Intervention Dose Considerations
Tumor Lysis Syndrome
Hydration
• Adults (NaCl 0.9%)
• Pediatrics (D5W-
NaCl 0.2-0.45%)
2-3 L/m2/day (200 mL/hr)
1.5-2x maintenance requirements
See table 1 for pediatric
fluid maintenance
requirements
Allopurinol
• Adults
• Pediatrics

300-600 mg/day
10 mg/kg/day in divided doses
Use IBW or AdjBW if ABW
>30% of IBW
Rasburicase 0.15 mg/kg (up to a max of 3 mg) Use IBW or AdjBW if ABW >30% of IBW
Hypercalcemia
Hydration
• Adults (NaCl 0.9%)
• Pediatrics (D5W-
NaCl 0.2-0.45%)
200-500 mL/hr
1.5-2x maintenance requirements
See table 1 for pediatric
fluid maintenance
requirements
Pamidronate
• Adults
• Pediatrics

60-90 mg
0.5-1 mg/kg (up to a max of 90 mg)
Should be administered
over at least 2 hours
Zoledronic acid 4 mg over 30-60 minutes Should be administered
over at least 15 minutes
Denosumab 60 mg or 120 mg

Calcitonin 4 units/kg Nasal calcitonin is not
recommended
Spinal Cord Compression
Dexamethasone
• Initial
• Maintenance

10 mg IV
16 mg/day in divided doses
Taper dose over 2 weeks
NaCl = sodium chloride; D5W = dextrose 5%
ABW = actual body weight; IBW = ideal body weight; AdjBW = adjusted body weight




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