Transcript 4- Extravasation and Chemoprotectant

Chemotherapy related
Toxicities and Management
Prof. Dr. Khaled Abulkhair, PhD
Medical Oncology SCE, royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University
Outlines
• Extravasation and its management
• Specific Chemotherapy Toxicities
and Chemo-protectants
• Management of Diarrhoea
• Dose Adjustments.
Extravasation
• Inadvertent administration of a vesicant
solution into surrounding tissue.
• Vesicant is a fluid or medication that on
extravasation can cause tissue necrosis.
• Best Example is Anthracyclines.
• Extravasations related to:
– Double puncture of the distal wall
– Mechanical friction
– Dislodgement of the catheter
Extravasations
• Signs and Symptoms
– Complaints of pain or burning
– Swelling proximal to or distal to the IV site
– Puffiness of the dependent part of the limb
– Skin tightness at the venipuncture site
– Blanching and coolness of the skin
– Slow or stopped infusion
– Damp or wet dressing
First signs are often subtle.
May be mild, blotchy redness, subtle
swelling or change in infusion rate.
Within days brawny discoloration,
indurations, dry desquamation,
blistering with discomfort and/or pain.
Full thickness skin necrosis that involves
underlying tendons and neurovascular
structures that leads to permanent damage.
Myelosuppression
Infection
Managing Extravasation
Stop infusion at once
Withdraw the drug
Leave cannula insitu
Elevate limb to reduce oedema
Apply heat for Vinca Alkaloids/and cold pack
for others including Anthracyclines Why?
• Subsequent management depends upon drug
involved and degree of damage. Maybe local
extravasation policy i.e. use of antidote.
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Antidotes
Drug
Antidote
Mechlorethamine
Na thiosulfate
Anthracyclines (Doxu, Dauno, Idaru,
Epirubi)
Dexrazoxane / +\- topical Dimethyl
Sulfoxide
Vinca Alkaloids
Hyalourinidase
Preventing Complications
• Ensure staff are trained and supervised
• Supervised practice and competence
assessed
• Practice continually updated
• Ensure correct preparation of patient,
equipment and environment
• Aseptic non touch technique
• Managed aftercare
• Documentation
Specific chemotherapy Toxicities and
Chemoprotectants
Each drug can cause a common and specific
toxicity that is unique to its family.
Chemotherapy
Type of Toxicity
Chemoprotectant
Anthracyclines
Cardiotoxicity
Dexrazoxane
Cisplatin
Nephrotoxicity/Ototoxicity Amifostine
Ifosfamide /
Cyclophosphamide
Haemorrhagic Cystitis
MESNA
Methotrexate
Mucositis/Nephrotoxicity
Glucarpidase
Leucovorin
Chemoprotectant
• Is a drug used to ameliorate specific toxicity
from chemo and or radiotherapy
• Characteristics:
 Easy to administer
Safe with no side effects
Prevents all toxicity
Doesn't interfere with the efficacy of
chemotherapy
Till date no this magic drug was not found
Dexrazoxane
• Acts as intracellular chelating agent thus decrease
Anthracyclines free radical damage.
• Approved in metastatic breast cancer to minimize
Cardiotoxicity if Anthracyclines cumulative doses
exceeds 300 mg.
• It may increase hematologic toxicity.
• Controversial data about decreasing
Anthracyclines effects, however, it is still indicated
for early curable breast cancer patients.
• Recently approved as an antidote in case of
Anthracyclines extravasation.
Amifostine
• It is used to decrease Cisplatin induced
nephrotoxicity.
• Also approved to decrease Xerostomia
with radiation therapy to H&N.
• Many side effects including allergic
reactions, nausea and vomiting and more
importantly hypotension.
Mesna (sodium di
mercaptoethane sulfonate)
• Detoxifies Acrolein by combining to it and prevents
it damaging the host cells.
• Acrolein is the active metabolite of both
Cyclophosphamide and Ifosfamide that causes
cystitis.
• Always given with Ifosfamide and may be used with
Cyclophosphamide if doses higher than 1500
mg/m2.
• Oral and injection formula are available; whatever,
the method to give should start before or with the
chemotherapy and ends few hours after it
Glucarpidase
• A carboxypeptidase enzyme, is now approved and indicated for the
treatment of toxic methotrexate concentrations (greater than 1
μmol/L) in patients with delayed methotrexate clearance due to renal
function.
• Administered as a single intravenous dose of 50 units/kg.
• Continue leucovorin until the methotrexate concentration has been
maintained below the leucovorin treatment threshold for a minimum
of 3 days.
• However, caution must be used with administering leucovorin in
conjunction with glucarpidase.
• Leucovorin should not be administered within 2 hours before or
after a dose of glucarpidase.
Management of Diarrhoea
• Intensive loperamide therapy using doses higher than the
recommended dose was initially described for irinotecaninduced diarrhoea.
• Atropine is used for the prevention of cholinergic activity of
acute irinotecan-induced diarrhea.
• There is no maximal dose of loperamide when using for
delayed diarrhea in this setting.
• The recommended dosing of loperamide is 4 mg P.O followed
by 2 mg every 2 hours until diarrhea free.
• Intensive antidiarrhea treatment is also used for other agents
(e.g., fluorouracil, epidermal growth factor receptor inhibitors).
CASES
A patient is receiving chemotherapy for limited-stage
small cell lung carcinoma. After the third cycle of
chemotherapy, she is hospitalized with febrile neutropenia.
She recovers, and today, she is scheduled to receive the fourth
cycle of chemotherapy. Which statement is the best treatment
course for this patient?
A. The patient should receive filgrastim 250 mcg/ m2/day
subcutaneously for 10 days.
B. The patient should receive filgrastim 5 mcg/kg/ day
subcutaneously, starting today.
C. The patient should receive pegfilgrastim 1 mg/ day
subcutaneously for 6 days.
D. The patient should receive filgrastim 5 mcg/kg/ day
subcutaneously for 7 days, given at least 24 hours after
chemotherapy
Which is the best sequence for
administering
Mesna
and
Ifosfamide?
A. Mesna before ifosfamide and then at 4 and 8
hours after ifosfamide.
B. Ifosfamide before mesna and then at 4 and 8
hours after mesna.
C. Mesna and ifosfamide beginning and ending at
the same time.
D. Mesna on day 1 and ifosfamide on days 2–5.
A 38-year-old woman has a history of Hodgkin
lymphoma. Two years ago, she completed six cycles of ABVD
chemotherapy (i.e., doxorubicin, bleomycin, vinblastine, and
dacarbazine). Each cycle included doxorubicin 50 mg/m2.
Recently, she was given a diagnosis of stage IV breast cancer.
She will be initiated on doxorubicin 50 mg/m2 and
cyclophosphamide 500 mg/m2 for four cycles. Which statement
is
most
applicable?
A. The patient has not reached the appropriate cumulative dose of
doxorubicin to consider Dexrazoxane.
B. The patient has reached the appropriate cumulative dose of
doxorubicin to consider dexrazoxane.
C. The patient should not receive any more doxorubicin because she is
at an increased risk of cardiotoxicity.
D. The patient should not receive dexrazoxane because of the
possibility of increased myelosuppression.
Sometimes, extravasation is not immediately
evident when it occurs. Immediately after
administering CHOP-R to patient 1 H earlier, an
extravasation is suspected. Which is the best
treatment recommendation for the patient’s
extravasation?
A. Application of a warm pack for suspected extravasation of
doxorubicin.
B. Application of a cold pack for suspected extravasation of
vincristine.
C. Application of dimethyl sulfoxide and intravenous
dexrazoxane for suspected extravasation of doxorubicin.
D. Application of sodium thiosulfate for suspected
extravasation of cyclophosphamide.
A 40-year-old man is about to begin R-CHOP chemotherapy
for large cell non-Hodgkin lymphoma. The patient asks how long the
treatment will take and whether he can be treated as an outpatient.
Which is the best answer?
A. Administration of this regimen is expected to be complete in 1 hour, but
because the regimen is highly emetogenic, it is usually given to patients
while in the hospital.
B. Administration of this regimen may take as long as 6 hours because the
rituximab infusion rate is slowly increased, but the regimen is usually
given to outpatients.
C. Administration of this regimen may take as long as 6 hours because the
vesicants doxorubicin and vincristine should be infused over several
hours, but the regimen is usually given to outpatients.
D. Administration of this regimen is expected to be complete in 1 hour, but
because of the risk of TLS, it is usually given to patients in the hospital.
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