Extravasation, hemorrhagic cystitis, TLS, hypercalcemia of malignancy Study Guide

Oncology Rat 15

What is extravasation (chemo-related)?

Leakage of cytotoxic chemotherapy from a blood vessel or tube into surrounding tissue

What is an irritant (chemo-related)?

Medication that when extravasated causes local inflammatory reactions at the infusion site

Common signs/symptoms of irritant extravasation?

1. Tender/Burning Vein

2. Swelling/Inflammation of the vein (ie. phlebitis)

3. Erythema 

4. “Tightness” around the administration site

5. Itching

What is a vesicant (chemo-related)?

Medication that when extravasated may cause severe or irreversible tissue injury and necrosis at the infusion site and surrounding tissue

Common signs/symptoms of vesicant extravasation?

1. Initial: Like what is seen with irritant

2. Blistering 

3. Pain around administration site

4. Severe: Necrosis/Tissue Breakdown

What factors affect extent of vesicant damage?

• Specific drug

• concentration

• length of exposure

• site of infiltration

What is a DNA-binding vesicant?

Vesicant binds to DNA of healthy cells in surrounding tissues causing apoptosis/cell death leading to continued dispersion & uptake into adjacent health cells

Example of a DNA-binding vesicant?

Doxorubicin

What is a non-DNA-binding vesicant?

Vesicant metabolized and neutralized in tissue causing less damage over time (gradual improvement)

Example of a non-DNA-binding vesicant?

Vincristine

How can extravasation be prevented?

• Established Protocols/procedures

• staff/patient education

• check blood return

• use central lines when appropriate

Why are central lines preferred for vesicants?

More durable access and rapid dilution in high blood flow vessels

First step in managing extravasation?

Stop infusion immediately

Should you flush the line during extravasation?

No

What should be done if possible after stopping infusion?

Aspirate drug via IV cannula

What should be done after catheter removal?

Elevate and immobilize the limb

When are cold compresses used for extravasation?

DNA-binding vesicants

• Ex: doxorubicin

How do cold compresses help?

Constrict blood vessels to prevent spread

When are warm compresses used for extravasation?

Non-DNA-binding vesicants

• Ex: vincristine

How do warm compresses help?

Increase blood flow to distribute and metabolize drug

What antidote is used for doxorubicin extravasation? What is the duration?

Dexrazoxane IV

• Duration: 3 days

How soon must dexrazoxane be given?

As soon as possible

• within 6 hours of extravasation

•  & at least 15min. after cold compress

What antidote is used for Vinctristine extravasation? What is the duration?

Hyaluronidase SubQ/Intradermal

What is the administration timing for Hyaluronidase SubQ/Intradermal?

ASAP

• Administered clockwise around the IV site in 5 separate injections

What is tumor lysis syndrome (TLS)?

Oncologic emergency caused by rapid tumor cell breakdown releasing intracellular contents into bloodstream

When does TLS usually occur after chemotherapy?

12 to 72 hours after chemo initiation

Can TLS occur without chemotherapy?

Yes, spontaneously in uncontrolled cancer

What intracellular contents are released in TLS?

Potassium, phosphate, purines, pyrimidines

• K⁺, PO₄^3-, Purines & Pyrimidines

Which cancers commonly cause TLS?

Leukemias and non-Hodgkin lymphomas with high tumor burden

What electrolyte abnormality occurs with potassium in TLS?

HYPERkalemia

What electrolyte abnormality occurs with phosphate in TLS?

HYPERphosphatemia

What electrolyte abnormality occurs with calcium in TLS?

HYPOcalcemia

Why does hypocalcemia occur in TLS?

Excess phosphate binds serum calcium and precipitates

• The ONLY electrolyte/metabolic abnormality that decreases

What uric acid abnormality occurs in TLS?

Hyperuricemia

What is laboratory tumor lysis syndrome (TLS)?

2 or more metabolic abnormalities occurring

• 3 days before OR

• 7 days after treatment

What defines clinical tumor lysis syndrome (TLS)?

• Laboratory TLS PLUS

• 1+ clinical implications (ex: increase in serum creatinine (SCr), cardiac dysrhythmia, seizure, or sudden death)

What is the metabolic abnormality associated with hypERkalemia in TLS?

K⁺ > 6mEq/L

• can lead to cardiac dysrhythmias and sometimes sudden death

What is the metabolic abnormality associated with hypERphosphatemia in TLS?

PO4^3- > 4.5mg/dL

• which can cause precipitation in blood and kidneys.

What is the metabolic abnormality associated with hypOcalcemia in TLS?

Corrected Ca²⁺ < 7mg/dL

• which can lead to cardiac dysrhythmias, seizures, neuromuscular irritability, and tetany.

What is the metabolic abnormality associated with hypERuricemia in TLS?

Uric Acid > 8mg/dL

• which can lead to acute renal failure from uric acid crystallization.

What is acute kidney injury (AKI) in the context of TLS?

• Increase in SCr > 1.5x ULN OR

• Oliguria (low OUP)

Identify major disease-related risk factors for TLS

• High tumor burden

• hematologic malignancies

  • Acute leukemias with high WBC

  • bulky lymphomas

• bulky solid tumors

Why does high tumor burden increase TLS risk?

More tumor cells = more intracellular contents released during lysis

Which acute leukemias are high risk for TLS?

ALL and AML

Which bulky lymphomas are associated with TLS?

DLBCL and Burkitt lymphoma

Which bulky solid tumors may cause TLS?

SCLC and germ cell tumors

Is TLS common in solid tumors?

No, it is less prevalent than in hematologic malignancies

What baseline patient factors increase TLS risk?

• Dehydration

• elevated uric acid

• elevated LDH

• baseline renal dysfunction

• Venetoclax use

Why does dehydration increase TLS risk?

Reduced renal perfusion and impaired clearance of solutes

Why does renal dysfunction increase TLS risk?

Kidneys cannot clear uric acid and excess electrolytes effectively

What does elevated LDH (lactate dehydrogenase) suggest in TLS risk assessment?

High tumor burden or rapid cell turnover

How is TLS risk reduced with venetoclax?

• Allopurinol prophylaxis

• ramp-up dosing

What is the general prevention strategy for TLS?

• Maintain kidney flow

• preserve urine output

• keep labs normal at baseline

Which nephrotoxic drugs may be held during TLS prevention?

ACE inhibitors and spironolactone

Why hold nephrotoxic drugs in TLS prophylaxis?

To reduce kidney injury and maintain clearance

Which drugs causing electrolyte abnormalities may be held in TLS prophylaxis?

ACE inhibitors and spironolactone

What IV fluid is commonly used for TLS prevention?

Normal saline

• Maintains adequate urine output and promotes renal clearance

What are xanthine oxidase inhibitors used for in TLS?

Maintain baseline uric acid and prevent further uric acid production

How do xanthine oxidase inhibitors work?

Block conversion of purines to uric acid

Do xanthine oxidase inhibitors lower existing uric acid?

No, they prevent new uric acid formation

First-line xanthine oxidase inhibitor for TLS prophylaxis? Dose?

Allopurinol

• 300 mg PO daily to 300 mg PO twice daily

When should allopurinol be started for TLS?

1 to 2 days before chemotherapy

How long is allopurinol continued in TLS prophylaxis?

Until TLS risk or presentation has resolved

Alternative xanthine oxidase inhibitor for TLS?

Febuxostat

What are indications for rasburicase in TLS?

• High TLS risk

• elevated baseline uric acid

• unable to tolerate allopurinol

How does rasburicase work?

Converts uric acid into soluble allantoin (an Inactive and soluble metabolite of uric acid)

Does rasburicase decrease uric acid production?

No, it lowers existing uric acid levels

Typical rasburicase dose for TLS?

3 to 6 mg IV once, may repeat based on uric acid levels

When should rasburicase be started before chemo?

4 to 24 hours before chemotherapy

How quickly does rasburicase work?

~4 hours

Main IV fluid treatment for established TLS?

IV normal saline

Why are loop diuretics used in TLS treatment?

Help clear excess electrolytes and uric acid

How is rasburicase dosed in TLS treatment?

Same dosing as prophylaxis

Does hypocalcemia in TLS always need direct treatment?

No, it often corrects after hyperphosphatemia is treated

When should hypocalcemia be treated in TLS?

Only if symptomatic

What severe TLS cases may require hemodialysis?

Cases with severe electrolyte abnormalities, fluid overload, or renal failure

What are the major pathological mechanisms of hypercalcemia of malignancy?

• PTHrP secretion

• osteolytic metastases

• tumor calcitriol production

What is the most common cause of hypercalcemia of malignancy?

Tumor secretion of PTHrP

What does PTHrP stand for?

Parathyroid hormone-related protein

How does PTHrP cause hypercalcemia?

• Increases bone resorption

• increases renal calcium reabsorption

• increases phosphate excretion

How does PTHrP affect bone?

Stimulates osteoclast-mediated bone breakdown releasing calcium into blood

How does PTHrP affect the kidneys?

Increases calcium reabsorption and phosphate excretion

Why does increased phosphate excretion raise calcium?

Lower phosphate levels are associated with higher serum calcium

• Inverse relationship

Which cancers are commonly associated with PTHrP-mediated hypercalcemia?

• Squamous cell carcinoma

• renal cancer

• breast cancer

What is the mechanism of osteolytic metastases causing hypercalcemia?

Bone destruction releases calcium into the bloodstream

Which cancers are associated with osteolytic hypercalcemia?

• Breast cancer with bone metastases

• osteosarcoma

• multiple myeloma

What are common mild symptoms of hypercalcemia?

1. Constipation

2. Fatigue

3. NA

4. Polyuria

What are common moderate to severe symptoms of hypercalcemia?

1. Lethargy

2. Confusion

3. Arrhythmias

4. Decreased consciousness

5. Bone pain

When is treatment indicated for moderate hypercalcemia?

Corrected calcium 12 to 14 mg/dL

When is treatment indicated for severe hypercalcemia?

Corrected calcium greater than 14 mg/dL

Why use corrected calcium in low albumin?

Low albumin lowers measured total calcium, so correction estimates true calcium

What is the corrected calcium formula?

Serum Ca + (0.8 x (4 - serum albumin))

If albumin is low, is measured calcium falsely low or high?

Falsely low

What is the general treatment approach for hypercalcemia of malignancy?

Treat the underlying cause FIRST

What is the mechanism of action (MOA) of IV fluids in hypercalcemia treatment?

Promotes renal calcium excretion and maintains urine output (UOP).

What is the first-line IV fluid used in treating hypercalcemia?

Normal saline (NS).

What role do loop diuretics play in hypercalcemia treatment?

May enhance calcium excretion if the patient is euvolemic.

What is the first-line IV bisphosphonate for hypercalcemia?

Zoledronic acid (Zometa), administered at 4 mg IV x1.

How does zoledronic acid work in treating hypercalcemia?

Inhibits bone resorption by stopping osteoclastic function.

What is the onset time for zoledronic acid to take effect?

24 to 72 hours, with the option to repeat in one week.