ONCOLOGIC EMERGENCIES Marti Larriva, PharmD

PGY1 Pharmacy Practice Resident

September 18, 2014

OBJECTIVES

•  Identify risks and benefits of MSCC therapy

•  Create a treatment plan for malignant

hypercalcemia

•  Identify risk factors for TLS and synthesize

appropriate prevention plan

OVERVIEW Importance, Definitions, & Types

A clinical condition resulting from a metabolic, neurologic, cardiovascular, hematologic and/or infectious change caused by that

to prevent loss of life or quality of life.

ONCOLOGY EMERGENCY

YOUR ROLE

Awareness

Prevention

Monitoring

Treatment

CLASSIFICATIONS

Metabolic

Structural

Treatment-Related

MALIGNANT SPINAL CORD COMPRESSION (MSCC) Back pain, paralysis, loss of bowel/bladder control

CASE 1 46 y/o female with stage IV breast cancer and no other significant PMH is admitted to your general medicine team s/p fall with cc: back pain, numbness/tingling and weakness in both lower extremities.

EPIDEMIOLOGY & PROGNOSIS Incidence of MSCC in terminal CA patients

5%

Lung

Breast

Prostate

NHL MM

RCC

Median Survival after Diagnosis < 6 months

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY Epidural Metastasis Compression & Venous Stasis

Interleukin and Prostaglandin Release

Vasogenic Edema

Ischemia

Neurologic Deficits

Glutamate Signaling

Cytotoxic Edema

Permanent Damage

TREATMENT Epidural Metastasis Compression & Venous Stasis

Interleukin and Prostaglandin Release

Vasogenic Edema

Ischemia

Neurologic Deficits

Glutamate Signaling

Cytotoxic Edema

Permanent Damage Recovery

Corticosteroids

Surgery

Radiotherapy

CORTICOSTEROIDS High Dose Dexamethasone Standard Dose Dexamethasone

96 mg IV bolus, 24mg PO q6h x 3 days , then taper

10 mg IV bolus, then 4 mg IV q6h, then taper

Adverse Effects Benefits

Psychosis

Infection

GI perforation

Severe Neuro deficits

RADIATION and SURGERY MSCC best treated with COMBINATION therapy

Radiation* Shrink the tumor!

Surgery Stabilize the spine

and/or resect tumor

*Chemotherapy may also be appropriate if the tumor is chemotherapy sensitive

RADIATION and SURGERY

CASE 1 46 y/o female with stage IV breast cancer and no other significant PMH is admitted to your general medicine team s/p fall with cc: back pain, numbness/tingling and weakness in both lower extremities.

CASE 1 On MRI the patient is found to have two separate lesions compressing both her thoracic and lumbar spinal cord. The patient was evaluated by Neurosurgery and is not a surgical candidate. What is the most appropriate course of therapy? A.  Furosemide 40mg IV q12h B.  Dexamethasone 4 mg IV q6h C.  Dexamethasone 4 mg IV q6h + Radiation therapy D.  Radiotherapy alone

HYPERCALCEMIA OF MALIGNANCY Bones, stones, groans, and psychological undertones

CASE 2

55 y/o male with HTN, DM and recently diagnosed prostate cancer presents with abdominal pain and confusion that has been ongoing for the past two days.

138 104 28

4.1 22 1.2 121

15.5 2.2

2.9

Albumin: 4.3 PTH: 12

Home Medications

Glipizide 5 mg daily

Metformin 1000 mg BID

HCTZ 25 mg daily

TUMS prn heartburn

EPIDEMIOLOGY & PROGNOSIS Patients experiencing hypercalcemia during

disease course

1/3

Breast Prostate

Renal Cell MM

T Cell Leukemia T Cell Lymphoma

Survived 30 days

Died after 30 days

Patients hospitalized for hypercalcemia

PATHOPHYSIOLOGY

PTHrP Vitamin D Bone

Metastasis

Released  from  tumor  

Osteoclast  stimulation  Absorption  Resorption  

Bone  store  release  

80%  of  cases  

Parathyroid hormone related peptide

Degrees of hypercalcemia

10.5-11.9mg/dL

Mild

12-13.9 mg/dL

Moderate

≥ 14 mg/dL

Severe

Corrected Calcium = Calcium + 0.8 (4-Albumin)

Confusion Lethargy

Coma Polyuria

Polydipsia N/V

Constipation

Bone Pain

Anorexia

Weight Loss Fatigue

TREATMENT

Stop calcium retaining products

Thiazides  Calcium  

Vitamin  D  Lithium  

 Fluids  +  Diuretics  

Calcitonin  Bisphosphonates  

Glucocorticoids  

Remove calcium from blood

TREATMENT

Glucocorticoids (3-5 days) Hydrocortisone 100 mg IV q6h

Prednisone 60 mg PO daily Usually limited to lymphomas

Bisphosphonates (48-72h) Zoledronic Acid 4 mg IV

Pamidronate 60-90 mg IV Caution: poor dentition (ONJ) or reduced CrCl

Calcitonin (12-24h) Calcitonin 4-8IU/kg IM/IV q12h Tachyphylaxis often occurs, IN ineffective

Diuresis (6-12h)

Lasix 20-40 mg IV q12-24h Avoid Thiazides

Hydration (6-12h*) NS 300-500cc/hr until euvolemic Caution: HF, Renal failure*

PTH

Monitoring

Potassium Magnesium Phosphate

Serum Creatinine

Urine output (I/O) Calcium Albumin

Ionized calcium

Therapeutic Efficacy Therapeutic Toxicity

CASE 2

55 y/o male with HTN, DM and recently diagnosed prostate cancer presents with abdominal pain and confusion that has been ongoing for the past two days.

138 104 28

4.1 22 1.2 121

15.5 2.2

2.9

Albumin: 4.3 PTH: 12

Home Medications

Glipizide 5 mg daily

Metformin 1000 mg BID

HCTZ 25 mg daily

TUMS prn heartburn

Which home medications would you

discontinue upon admission?

CASE 2

The patient has already been started on NS running at 300mL/hr, what would be the next step in treatment and what would you monitor? A.  Hydrocortisone 100 mg IV q6h; Monitor Ca, K, Mg B.  Furosemide 40 mg IV q24h; Monitor Ca, K, Mg, SCr C.  Zoledronic Acid 4 mg IV x 1; Monitor Phos, Ca D.  Dialysis; Monitor Ca E.  B and C

TUMOR LYSIS SYNDROME

Renal failure, Arrhythmia, Seizures

http://circ.ahajournals.org/content/116/1/e2/F3.expansion.html  

CASE 3

52 y/o female patient admitted for new onset acute myeloid leukemia who will be started on hydroxyurea to decrease her WBC prior to starting induction chemotherapy. Below are her baseline lab values: 137 100 26

3.4 28 2.3 181

7.2 2.2

2.6

Uric Acid: 5.9 Albumin: 2.3 LDH: 500

7.6

25.9 187 44

Epidemiology & Prognosis

Cancer  Mass  

Bulky  or  metastatic  

Organ  involvement  

Lysis  Potential  

Proliferation  Rate  

Cell  Sensitivity  

Chemo  

Intensity  

Patient  Factors  

Renal  Impairment  

Hypotension/Volume  depletion  

Nephrotoxins  TLS é  Risk of death during

treatment and é LOS

Pathophysiology

TLS Induced Renal Failure

Definition

SCr ≥ 1.5 x ULN Cardiac arrhythmia

Seizure Sudden death

Uric Acid ≥ 8 mg/dL Potassium ≥ 6mEq/L

Phosphorous ≥ 6.5 mg/dL Calcium ≤ 7 mg/dL

OR a 25% change from baseline

Cairo-Bishop Laboratory TLS

Clinical TLS

≥ 2

Treatment Strategies

Prevention

Evaluate risk factors

1)  Tumor burden

2)  Sensitivity

3)  Underlying dysfunction

Determine and

of prophylaxis

Treatment

Manage lab abnormalities

–  Hyperkalemia

–  Hyperphosphatemia

–  Hyperuricemia

Dose adjust medications

based on function

Prevention

Prevention

• NS IV 2500-3000mL/m2/day

• Goal: UO = 80-100 mL/m2/hr Hyperhydration

• 300 mg/m2/day starting 48h prior to chemotherapy

Allopurinol

• 0.15-0.2 mg/kg IV x 1 then reassess

Rasburicase

Caution:  Heart  or  Renal  failure  

No  need  for  renal  dose  adjust  

Ensure  proper  G6PD  function  

Risk Stratification Low Intermediate High

Solid Tumors*

Multiple Myeloma

*Exception: Germ cell cancer OR small cell

lung cancer

Leukemia/Lymphoma

Less aggressive Indolent   Elevated LDH>2x ULN

Elevated WBC>25  

Burkitt’s Lymphoma

 

Prevention Low Intermediate High

prn Normal

Hydration

Monitor

Hyper-hydration

Allopurinol

Monitor

*prn loop diuretic

Hyper-hydration

*prn loop diuretic

Allopurinol OR

Rasburicase

Monitor

Treatment Strategies

Prevention

Evaluate risk factors

1)  Tumor burden

2)  Sensitivity

3)  Underlying dysfunction

Determine and

of prophylaxis

Treatment

Manage lab abnormalities

–  Hyperkalemia

–  Hyperphosphatemia

–  Hyperuricemia

Dose adjust medications

based on function

Hyperkalemia Potassium (3.7-5.2 mEq/L) Mild: 5.5-6.5 Moderate: >6.5 Severe: >6.5 + ECG changes

Stabilize Myocardium

•  Calcium gluconate 1-2 g IV over 5-10 mins, may repeat

Shift Potassium

•  Insulin 10 units + D50W 50mL IVP •  Albuterol 10-20 mg nebulized over 10 mins

•  Sodium bicarbonate 50-100mEq IV over 2-5 mins

Remove Potassium

•  Lasix 20-40 mg IV •  SPS 15-60 gm PO q6h

   

Hyperphosphatemia Phosphate (2.4-4.1 mg/dL) Ca x Phos > 70

Phosphate Binders (prevent absorption via GI tract)

Aluminum Hydroxide 300 mg PO with meals

Calcium Acetate 1337 mg PO TID AC

Sevelamer 800-1600mg PO TID AC

ê Calcium

êRenal fxn

éCa

Hyperuricemia Uric Acid Low <4 Intermediate: 4-8 High >8

   

Flush out uric acid

• NS 2500-3000mL/m2/day

• Goal: UO = 80-100mL/m2/hr

Metabolize Uric Acid

• Rasburicase 0.2 mg/kg IV x 1, redose based upon UA levels

Acute Renal Failure

Dialysis if:

1)  No response to fluids

2)  Volume overload

3)  Hyperkalemia despite treatment

4)  Phosphate > 10.2mg/dL +

symptomatic hypocalcemia

First line: Hyperhydration

NS IV 3L/m2/day Goal UO 80-100mL/m2/hr

CASE 3

52 y/o female patient admitted for new onset acute myeloid leukemia who will be started on hydroxyurea to decrease her WBC prior to starting induction chemotherapy. Below are her baseline lab values: 137 100 26

3.4 28 2.3 181

7.2 2.2

2.6

Uric Acid: 5.9 Albumin: 2.3 LDH: 500

7.6

25.9 187 44

Ht: 149.9 cm Wt: 99.9 kg

CASE 3

Based upon her baseline lab values and risk for TLS what preventative regimen should she be placed on? A.  Intermediate Risk (hyperhydration + allopurinol) B.  Low Risk (normal hydration) C.  High Risk (hyperhydration + rasburicase OR

allopurinol)

Why did you choose

this answer?

Take Home Points

1) MSCC should be treated initially with steroids (dexamethasone), but with radiotherapy and surgery is more effective overall.

2) HOM is best treated with to

decrease calcium in the acute setting, but are first line to obtain

normocalcemia over the coming weeks and should be started concomitantly.

3) Severity and occurrence TLS can be reduced through

adequate and treatment prior to chemotherapy.

Other Oncologic Emergencies

Metabolic

SIADH

Structural

Pericardial Effusion

Superior Vena Cava Syndrome Increased ICP

Treatment-Related

Neutropenic Fever Hypersensitivity

Hematologic

Hyperviscosity

Questions?

marti.larriva@ucsf.edu

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