Transcript 1- Oncology Emergencies

Oncologic Emergencies
Prof. Dr. Khaled Abouelkhair, PhD
Medical Oncology SCE, Royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University, Egypt
• Hypercalcemia
• Hyperuricaemia / TLS
• Cord Compression
Drugs…errors and prevention
Health care is committed to patient’s
safety… so why
Too many medical errors do occur
everyday
Imipenem 1000 mg I.V q 6h in a
patient with renal impairment.
• How many errors in this prescription?
• What is the maximum dose of Imipenem in
such situations with renal impairment?
• When this error was discovered I realized why
western countries always emphasis that we
should always have a good system to follow
doing our job rather than depending on
individual expertise.
On Thursday 4th January 2001, A Mr WJ, a day case patient
at the Queen’s Medical Centre Nottingham U.K, was
prepared for an IT administration of chemotherapy as part
of his medical maintenance program following successful
treatment of leukemia.
After carrying out a lumbar puncture and administering the
correct cytotoxic therapy (Cytosine) under the supervision
of the Specialist, Dr Morton, a Senior House Officer, was
given a second drug administer to Mr WJ, which he
subsequently did.
However, the second drug, Vincristine, should never be
administered by the intrathecal route because it is
almost always fatal.
This is just a single example for too many daily errors that
could happen.
Deadly Story of Medication Errors
Pilot study in 2 London hospitals:
Adverse
events in
>1 in 10 pts
1/3 of these
are serious
What is clear is that we need to know more
about errors and do more about them
Sir George, BMJ March 2002
Trajectory
Most errors result from multiple contributing failures (holes). The
trajectory path shows that several layers of protection had been lost
increasing the likelihood of harm to occur. No one is immune.
Pharmacist
Lab.
Administration
Oncologist
Fatal Error
How could that apply to Oncology?
Simply we can kill our patients
ONCOLOGIST ERRORS
 Lack of experience..
 Work load
 Improper protocol..R-CHOP for H.D
 Serious combinations…NSAIDS + HDMTX
 Unawareness of co-morbidities.. H.F, CRF
 Unawareness of drug side
effects..Allergies…..examples…premedication
 Dose modifications
 Premedications and post chemotherapy treatment
A good pharmacist always review the drugs, doses, dose
reductions, number of cycles and appropriate protocols.
PHARMACIST ERRORS
 Who can tell me…..?
ALWAYS WATCH THE OTHERS’ MISTAKES
 If the pharmacist layer failed to correct other’s
mistakes……this is a fatal error.
 Always remember pharmacists are our safe guards
coming in the middle between prescription and
administration
What you should check for?
The Simple Five Rules R’s
 Right Patient
 Right Drug
 Right Dose
 Right Route
 Right Time
Take Home Messages
 We are dealing with serious drugs for serious disease
affecting miserable patients…
Please don't add to their misery.
 Remember your safety layer….
Close any holes that could be there
 As being oncologists, we always depend up on you to catch
on and correct our mistakes..
Please do not fail us.
• A patient admitted in the medical floor, known
case of lung cancer metastatic to bone, the nurse
reporting that the patient is Lethargic, stupor, as
well as Fatigue, Dehydration and constipation.
ECG was requested which revealed Cardiac
bradycardia, and short QT interval
• What would it be?
• Metabolic or Neurologic?
The calcium ion plays a critical role in normal
cellular function and signaling (neuromuscular
signaling, cardiac contractility, hormone secretion,
and
blood
coagulation).
• Feedback mechanisms maintaining extracellular
calcium concentrations within a narrow,
physiologic range.
• Normal Ca level (8.9 – 10.1 mg/dl).
• Corrected Ca mg/dl = (4- albumin in g/dl) x 0.8 + serum Ca.
• Commonest Cancer NSCLC, SCLC, Breast, M.M,
RCC, and NHL (T-cell).
• Causes of Hypercalcemia:
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Direct bone destruction
Immobilization
Parathormone like hormones
Medications e.g. Thiazides, Antiestrogens, Vit A
Excessive calcium intake, milk alkali syndrome
Management
• First be sure it is true hypercalcemia?
• The second most important laboratory test in
the diagnostic evaluation is a PTH level.
• Serum creatinine should be measured to assess
renal function.
Mild Hypercalcemia: asymptomatic patients with
minimally elevated calcium levels (< 12.0 mg/dL)
…Encouragement of oral hydration, mobilization, and
elimination of drugs that contribute to hypercalcemia
are essential. 2-3 L of intravenous fluid may be required
over the first 24 h
• Moderate Hypercalcemia: 12 -14 mg/dl
symptomatic directed therapy.
• Severe Hypercalcemia: ≥ 14 mg/dl. Emergency
– Hydration 3-6 L/24h.
– Loop diuretics. Furosemide, 20 to 40 mg IV, may
be initiated after volume expansion is achieved, with
subsequent doses given when urine output is < 150
to 200 mL/h. Thiazides are contraindicated.
– Bisphosphonates. Onset of action 2-4 days.
– Calcitonin. Rapid onset 2-4 Hours, peak effect in 48
hours, short lived effect. Dose 4-8 IU/Kg S.C Q12h.
Works through inhibiting the effects of parathyroid
hormones.
– Corticosteroids: only in steroid responsive tumours
– Phosphate: rarely used for fear of soft tissue
precipitations.
– Cyclo - Oxygenase inhibitor: Indomethacin, rarely
used if other drugs fail.
– Dialysis: if renal failure is not improving with
hydration and emerging volume overload.
• Prevents bone resorption.
• Side Effects: Flu like symptoms, Nausea and
vomiting 46%, Fatigue 39%, Fever 32%, Diarrhea
24%, Arthralgia/ myalgia 23%, and deterioration of
renal function.
• Delayed onset of action 48 – 72h.
• 4mg IV infusion over 15 minutes following
rehydration. May repeat after 7 days if not normocalcemic and can tolerate hydration.
• Remember dose reduction based on creatinine
clearance.
Denosumab: Fully human monoclonal antibody that targets
and inhibits RANKL, a protein that acts as the primary signal
to promote bone removal
Indication: Prevention of skeletal-related events in patients
with bone metastases from solid tumors
Dose: 120 mg subcutaneously every 4 weeks
Adverse events: Urinary and respiratory tract infections,
cataracts, constipation, rashes, and joint pain
Contraindications: Hypocalcemia. Patients should be taking
calcium and vitamin D.
No adjustment for hepatic or renal dysfunction is needed.
• No Diuretics without Hydration in
Hypercalcemia.
• Always check creatinine clearance and adjust
doses, if using Bisphosphanates.
• Be aware about renal toxicity of Bisphosphanates
and renal doses.
• Calcitonin lost its effect after 2-3 days.
• Review medications and stop agents, if feasible,
that may cause hypercalcemia and/or renal
impairment.
• It’s a rapid development of metabolic
abnormalities accompanying the release of
intracellular contents into the bloodstream due to
tumor cells death.
• Rapid release of intracellular contents can
happen spontaneously with high tumor burden or
from cell lysis due to cytotoxic agents (even
steroids!), cytokine or hormonal therapy .
Aetiology:
 A–Diseases:
a –Leukemia
- Acute and CLL
b–Lymphoma
- Burkitt’s
- T- Cell
- Lymphoblastic
c –Solid tumor
- Neuroblastoma
- SCLC - Breast Cancer
 B - Large tumor burden:
- Stage IV extensive rapidly dividing tumors
Precipitating Factors:
- Spontaneous
- Commencing treatment
Co-factors:
- Pre-existing renal insufficiency
- hyperuricemia
Metabolic Abnormalities:
• Tumor cells contain a high concentration of
potassium and phosphate. Their rapid breakdown
will release these electrolytes into the blood
resulting in:
Hyperkalemia, Hyperuricaemia,
Hyperphosphatemia and hypocalcaemia
• Soft tissue calcium phosphate deposition and
hypocalcaemia occur as a result of calcium downregulation secondary to Hyperphosphatemia
• Renal failure is a common complication.
Presentation:
• Many are asymptomatic
• Symptoms’ severity reflects the underlying
metabolic abnormalities.
1- Hyperkalemia: life-threatening, ventricular
dysrhythmias, paresthesia and weakness.
2- Hyperuricaemia: may lead to arthralgia and
renal colic, urate nephropathy, fatigue, weakness
etc… the worst ARF.
3- Hypocalcaemia: Neuromuscular instability with
muscle cramps, tetany, anxiety, carpopedal
spasms, bronchospasm, confusion and
convulsions.
ARF in TLS
Management
Prevention
Once occurred ARF is a major problem with
serious consequences.
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Fix conditions that will make effects worse . NSAIDs
Get baseline labs: K, Ca, Phos, Uric Acid, LDH, Cr.
Preventing renal failure and severe electrolyte imbalances.
Increase urine production with proper hydration.
Decrease uric acid concentrations using Allopurinol
(Competitive inhibitor of xanthine oxidase) which decrease
uric acid synthesis from Purines but limited efficacy.
 Alkalinize urine keeping PH above 6.5 as Uric acid > 10x’s
more soluble in pH of 7.0 compared to pH of 5.0.
If occurred….
• Continue the same measures Plus
• Manage ARF
• Magic Drug RASBURICASE (recombinant urate oxidase)
promotes catabolism of uric acid  Allantoins (10x more
soluble than uric acid).
What are the differences between
Allopurinol and Rasburicase
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Oral versus IV
Prevention and treatment
Nephrotoxic
Needs dose adjustment
Fast action
Drug - drug interactions
Inhibits Enzymatic reactions or an enzyme
Readily revert metabolic abnormalities including
ARF
• Needs alkalinisation
Cord Compression
• 2-5% of cancer patients have an episode of SCC
• Commoner in myeloma, prostate, lung and breast
cancer (15-20%)
• 10% of patients diagnosed with SCC may have a
second episode.
• Presentation Depends on level (77% in T spine).
• Radicular back pain in 85-95%.
• Worsened by lying flat, weight bearing, coughing
and sneezing, relieved by sitting.
• Managed by Steroids, surgery and Radiation.
Methotrexate Toxicity
• Leucovorin Rescue ??? Methotrexate Toxicity.
• Factors that increase Methotrexate Toxicity:
– Renal impairment
– Third space fluid
– Drugs e.g. penicillin, NSAIDS, PPIs etc.
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Safe Methotrexate level 0.05 – 0.1mM.
Any MTX doses above 500 mg/m2 needs rescue.
Remember alkalinisation.
Leucovorin and Fluorouracil???
Glucarpidase
- A carboxypeptidase enzyme, is now approved and indicated
for treating toxic methotrexate concentrations (greater than
1 μmol/L) in patients with delayed methotrexate clearance
due to impaired renal function.
- A single intravenous dose of 50 units/kg with 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.
Case I
A 20-year-old man was recently given a diagnosis of acute
non–lymphocytic leukaemia. His white blood cell (WBC)
count is 35 × 103 cells/mm3, and he will receive chemotherapy
tomorrow. Which is the best prevention strategy for tumor lysis
syndrome (TLS)? .
A. Hydration with 5% dextrose (D5W), 1 L before chemotherapy,
plus allopurinol 300 mg/day.
B. Hydration with D5W, 100 mL/hour starting at least 24 hours
before chemotherapy, plus allopurinol 300 mg/day.
C. Normal saline 100 mL/hour starting at least 24 hours before
chemotherapy plus allopurinol 300 mg/day.
D. Hydration with normal saline 100 mL/hour starting at least 24
hours before chemotherapy plus NaCO3 500 mg orally every 6 H.
Case II
A 65-year-old man with metastatic non–small cell
lung cancer is brought to the clinic by his family because
of alterations in his mental status. Pertinent laboratory
values include a serum calcium concentration of 12 mg/dL
and an albumin concentration of 2 g/dL. Which therapy is
best for this patient’s altered mental status?
A. Calcitonin 4 units/kg every 12 hours.
B. Furosemide 20 mg orally.
C. Dexamethasone 10 mg orally two times/day.
D. Zoledronic acid 4 mg intravenously.