Chemotherapy Emergencies

Episode Notes

Infusion Reactions and Hypersensitivity

1. Symptoms (least to most severe): fatigue, myalgias, fever, and headache; rash, urticaria, pruritus, and flushing; nausea, vomiting and abdominal pain; dyspnea, throat irritation, laryngeal edema, and bronchospasm; and dizziness, hypotension, and tachycardia

2. Immediate reactions (~5-10 min) usually due to diluent or formulation vs later onset (~30 min in) are true hypersensitivity to the drug, although there is some overlap

3. Avoidance

1. Premedication with corticosteroids, H1 and H2 blockers

1. Give 30 minutes prior to infusion

2. If prior reaction -> give for 24 hrs prior to desensitization

4. Immediate Infusion Reaction

1. Offending Agents: Paclitaxel (cremophor), docetaxol, liposomal doxorubicin, rituximab

1. Taxol hypersensitivity reaction generally due to cremophor (solvent used) and occur during 1st or 2nd exposure

2. Common symptoms: sensation of a “hot seat” - pressure/heat sensation, as if they immediately need to urinate, flushing, chest pain, abdominal or back pain, increase in heart rate or change in blood pressure

3. Signs/symptoms typically improve/resolve when infusion is stopped

4. Management: stopping the infusion, giving additional doses of IV antihistamine/steroids, waiting 30min - 1 hour until symptoms resolve, and then re-challenging by slowly increasing titration of the infusion rate in fifteen-minute intervals as tolerated

5. Consider switching to alternative therapy (i.e. paclitaxel -> albumin bound paclitaxel (abraxane))

5. Hypersensitivity

1. Cisplatin and carboplatin common

1. Risk of reaction increased with increased cumulative exposure

2. Other offending agents: paclitaxel, docetaxel, etoposide, topotecan

3. Signs/symptoms typically continue and even worsen after the chemotherapy infusion is stopped

4. Management: 

1. stop the infusion (confirm pump turned off)

2. assess ABCs (airway, breathing, circulation), apply oxygen

3. If severe anphlaxis/angioedema -> IM epinephrine

4. benadryl 50 mg IV x 1 STAT for H1 blockade, 20 mg famotidine IV for H2 blockade, IV normal saline bolus for BP support 

5. give corticosteroids - dexamethasone 20 mg IV, methylprednisolone 125 mg IV, or hydrocortisone 100 mg IV

6. If symptomatic wheezing -> nebulized beta-agonist bronchodilators

7. Observe for >= 1 hr before leaving

8. If symptoms worsening/persistent -> give another 20 mg IV dexamethasone or corticosteroid equivalent

9. Patient is done w/ chemo for the day!

5. Future Management

1. If mild reaction → can be rechallenged in 3-5 days time using a desensitization protocol. This involves a 4-bag protocol with simple dilutions from the original bag 1:1000, then 1:100, then 1:10, and finally 1:1.  

1. Each bag is given over 1 hour, with the exception of paclitaxel which is 3 hours per bag.

2. If severe reaction (hypotension, systemic urticaria, intubated, coded) → do not rechallenge and refer to allergist

6. If in doubt… treat as hypersensitivity

1. Stop the infusion, give additional doses of IV anti

2. SGO ConnectEd one-page reference: Management of Chemotherapy Hypersensitivity Reactions and Desensitization

1. Febrile Neutropenia

1. Infectious Diseases Society of America definition: temp >= 38.3C (101F)  x 1 or a sustained temperature of >= 38C (100.4) for an hour PLUS an absolute neutrophil count (ANC) < 500 or an ANC that is expected to drop to below 500 in the next 48 hours

2. Neutropenia definitions

1. Mild: ANC < 1500

2. Moderate: ANC < 1000

3. Severe: ANC < 500

4. Profound: ANC < 100

3. Risk increases significantly with ANC < 500 or sustained > 7 days

4. May not be able to mount a fever, so look for other signs of SIRS too (tachycardia, tachypnea, hypotension)

5. Identify early!

1. mortality ranges from 5-20%, and climbs to 50% in patients experiencing shock.

6. Can be due to bacterial or fungal source

7. Try to get blood cultures before antibiotics, but don’t delay - administration within 30 minutes improves survival rates

8. Empiric therapy w/ anti-pseudomonal beta-lactam preferred; if MRSA likely, add vancomycin

9. Is this an emergency though?

1. Validated scoring systems

1. Clinical Index of Stable Febrile Neutropenia (CISNE)

2. Multinational Association for Supportive Care in Cancer (MASCC) Index for Febrile Neutropenia

2. High risk warrants inpatient management

1. neutropenia suspected to last > 7 days, if they have a MASCC score < 21 or a CISNE score >= 3, if there are signs of severe sepsis or septic shock, mucositis that interferes with swallowing or causes severe diarrhea, GI symptoms, intravascular catheter infection, new pulmonary infiltrate or hypoxemia, underlying chronic lung disease, cancer that is progressive after 2 cycles of chemotherapy, hepatic insufficiency (AST or ALT > 5x upper limit of normal), and/or renal insufficiency (CrCl < 30)

3. If being managed outpatient… daily evaluation x 72 hours, return if develop new signs or symptoms, or persistent/recurrent fever after 3-5 days

4. Role for G-CSF?

1. Infectious Diseases Society of America recommends against it

2. ASCO and NCCN guidelines say they can be considered for patients at high risk for infection-associated complications or if have factors predictive of poor clinical outcome

5. Length of antibiotic use?

1. If find source → treat infection as dictated by site and infectious agent

2. No source → continue empiric abx until afebrile x 72 hrs and no longer severely neutropenic

2. Drug Extravasation

1. Definition: leakage of fluid or medication from a blood vessel into the surrounding tissues

2. Vesicants are highest risk followed by irritants

3. Vesicants

1. Potential to cause blistering, severe tissue injury, and/or tissue necrosis

2. Offending agents: doxorubicin, actinomycin D, cisplatin at some concentrations, trabectedin and vinorelbine

3. Some advocated for central venous access via Mediport when using these 

4. May need management with plastic surgery - debridement often needed for unresolved pain/necrosis persisting longer than 10 days

4. Irritants

1. Localized reaction including aching, tightness, plebitis, inflammation

2. Offending agents: carboplatin, gemcitabine, liposomal doxorubicin, bleomycin, etoposide, ifosfamide, and topotecan

1. Paclitaxel and docetaxel are irritants with some vesicant-like properties

5. Signs

1. Early: discomfort, burning, erythema, leakage from the IV site, or slow infusion

2. Late: more severe pain, swelling that progresses to blanching or blistering, discoloration, and/or necrosis

6. Management

1. stop the infusion immediately, keep the cannula in place, aspirate the extravasated fluid

2. Don’t flush the line!

3. Specific protocols and antidotes per drug

1. Table 12.2 in the Principles of Antineoplastic Therapy, 4th Edition, published on SGO Connect Ed.

3. Hemorrhagic Cystitis

1. Offending agents: cyclophosphamide, ifosfamide

1. Prodrug with hepatic metabolism; acrolein generated as byproduct; excreted in urine and directly damages the bladder mucosa

2. Prevention

1. IV hydration 12-24 hrs before treatment, continued 24-48 hrs after at rate of 2x maintenance

2. Mesna (sodium 2-mercaptoethane sulfonate) co-administered w/ chemo and then 2 and 6 hrs later

1. Binds acrolein in urine w/o affecting antitumor activity of the chemos

3. Management

1. If severe, can lead to clot formation and bladder outlet obstruction

1. Consult urology and consider 3-way continuous bladder irrigation

4. Anemia

1. Multifactorial, but in general, transfuse if < 7 and don’t if > 10; space in between is a judgement call

2. Erythropoiesis stimulating agents no longer used or recommended

1. associated with an overall increased risk of death, MI, stroke, and other cardiovascular events.  In some oncologic RCTs, were linked with disease progression and decreased OS

5. Thrombocytopenia

1. Defined as plt < 150k

2. Commonly seen w/ carboplatin and PARP inhibitors

3. Thresholds for transfusion

1. If bleeding or open procedure planned → transfuse to > 50k

2. If DIC or intracranial bleeding → transfuse to > 100k

3. If < 10k w/o bleeding → transfuse (increased risk of spontaneous hemorrhage)

4. Thrombopoietin receptor agonists (TPO-RAs) controversial

1. Can be considered for chemo-induced thrombocytopenia but aren’t FDA approved for this indication

2. May have an increased risk of VTE

3. Don’t give w/o guidance from hematology

6. Leukopenia

1. NCCN, ASCO, EORTC recommend G-CSF prophylaxis if risk of developing febrile neutropenia > 20%

1. Usually not w/ first cycle, but consider in future if h/o neutropenic fever or delays d/t neutopenia

2. G-CSF Toxicities

1. Mild to moderate bone pain - manage w/ NSAIDs and antihistamines

2. Severe: splenic rupture, increased risk of bleomycin pulmonary toxicity

3. Consider dose reduction instead!

1. Guidelines for each drug on how and when to dose reduce available

7. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

1. Body makes too much ADH (vasopressin) leading to excessive water retention and low sodium levels

2. Offending agents: platinum compounds, alkylating agents such as ifosphamide and cyclophosphamide, vinca alkaloids

3. Labs: Na < 135, decreased serum osmolarity, concentrated urine

4. Management

1. Fluid restriction, slow correction of serum sodium