Complications of Cancer and Chemotherapy Flashcards
What is SVCO, and how can it come about due to cancer?
- Superior Vena Cava Obstruction (SVCO)
- Narrowing or occlusion (blockage) of the SVC
- Obstructs venous return to the right side of the heart
Reasons:
> External compression; tumour (in close proximity)
> Thrombus; more likely in cancer (inflammatory cascade activation, predisposed to clots)
Which cancers are often responsible for SVCO?
- Carcinoma of the bronchus (80% of cases; SCLC > NSCLC)
- Lymphoma, germ cell tumours, mesothelioma (asbestos-induced) and thymoma (chest & thymus gland) may also be responsible
What are the signs and symptoms for SVCO?
SVCO blocks drainage of upper body (H&N):
- Oedema: face, neck, arms
- Fixed engorged jugular veins (increased JVP); veins stand out on neck
- Dilation of superficial skin veins; head, neck, chest
- SOB or stridor (noisy breathing)
- Cyanosis (venous congestion; looks blue)
- Cough, hoarse voice
- Headache, confusion (intracranial venous congestion = increased intracranial pressure)
What investigations are undertaken as a result of SVCO?
- Chest X-ray (looking for mediastinal mass)
- CT scan/MRI of chest; defining extent of disease, assisting RT planning.
- Venography; dye injected to see how occluded SVC is
- Biopsy; establish diagnosis if initial presentation, assists treatment decisions
What is the acute treatment for SVCO?
Corticosteroids
- High dose dexamethasone (8mg BD)
- Reduces swelling and pressure around vessel, as well as oedema
Vascular stenting (within 2-3 days) - Particularly if urgent symptom relief required
What is the definitive treatment for SVCO?
- Radiotherapy (2-3 weeks before effect seen)
- Chemotherapy (if chemo-sensitive tumour; biopsy)
- LMWH; treatment for thrombus if indicated (1.5 mg/kg OD)
What is the Pharmacist’s role in SVCO treatment? (Corticosteroids? LMWH?)
Corticosteroids:
- Given promptly
- Timing of dose (steroids compromise sleep so no systemic dosing; morning and 2PM instead)
- PPI cover if appropriate for duration of steroids ONLY
- Dose review/reduction
- Blood glucose monitoring
LMWH:
- Dose recommendation
- Conversion to warfarin if appropriate; but a lot of patients stay on enoxaparin instead (INR difficult to keep in range w/warfarin w/chemotherapy patients; inflammatory cascade etc.)
WHat is SCC, and what is the source?
- Spinal cord compression
- Mainly occurs where bone metastases are common; prostate, breast cancer etc.
- Results from pressure on spinal cord:
> Tumour/bone metastases growing directly between vertebral bodies
> Crush fracture/collapse from vertebral metastasis
> Intramedullary metastases causing acute compression from within (rare) - Can be first presentation of cancer
- Most common in thorax (high up)
What are the signs and symptoms of SCC?
- Onset can be gradual or acute; e.g. not managing stairs well, difficulty passing urine, numb areas leg/feet
- Depend on site of compression; low down = bladder/leg, thorax = coughing, deep breaths
- Pain at level of compression and movement
- Motor weakness; can’t walk as far, stairs hard, numb
- Sensory loss (numb)
- Bladder/bowel dysfunction
- Cauda equina; pressure on bottom of spinal cord = sacral anaesthesia, urinary retention, erectile dysfunction
What investigations are undertaken for suspected SSC?
Urgent whole spine MRI scan:
- Detects level of compression
- Definitive; know exact cause
- Allows planning of RT/surgery
Plain X-ray:
- May show evidence of bone metastases, mass or crush fracture at site
How is SCC treated acutely?
Corticosteroids (within 24 hours):
- Dexamethasone 8mg BD (similar to SVCO)
What is the definitive treatment for SCC?
Radiotherapy; symptomatic; as dead nerves in spinal cord do not regenerate.
- Days-weeks for effect; titrate steroids down upon improvement
Bedrest (flat)
- Until possibility of spinal instability discontinued
- Eat, drink etc. all FLAT; “long-rolling” of patient like spinal may be required.
Symptom management:
- Catheterisation
- Analgesia
- Bowel mangement
When is surgery an option for SCC?
- If spine unstable (tumour eaten away vertebrae); risk of severing cord, put wires/rods in to protect nerves
- If insensitive to RT (e.g. melanomas)
- Unknown tissue diagnosis; biopsy
What are the prognostic signs for SCC?
- Linked to onset and duration of symptoms
- Prompt diagnosis and treatment vital
> Ability to walk at diagnosis indicative to overall survival
> Loss of sphincter function at diagnosis; indicative of delayed presentation, bad prognostic sign.
What is the pharmacist’s role w/SCC treatment?
Corticosteroids:
- Given promptly
- Timing of dose (steroids compromise sleep so no systemic dosing; morning and 2PM instead)
- PPI cover if appropriate for duration of steroids ONLY
- Dose review/reduction
- Blood glucose monitoring
DVT/PE (pulmonary embolism) prophylaxis:
- Pressure stockings, enoxaparin 40mg OD
Analgesia
What is TLS, and how can it manifest?
Tumour lysis syndrome
- Group of metabolic disturbances
- May occur before or after start of chemo; large tumour burden, high proliferative rate and high chemosensitivity
- Rapid destruction of malignant cells = release of intracellular contents = acute metabolic disturbance
Manifests as: > Hyperuricemia > Hyperphosphataemia > Hyperkaleamia > Hypocalcaemia
How does TLS present (signs/symptoms)?
Biochemical disturbances can cause:
- Nausea
- Diarrhoea
- Muscle weakness (hypocalcaemia)
- Tetany; intermittent muscle spasms (hypocalcaemia)
- Seizures (electrolyte imbalances)
- Arrhythmias (hyperkalemia)
- Renal failure
- Sudden death
What is the pathophysiology of TLS?
48-72 hours following chemotherapy (can be spontaneous):
Uric acid; from breakdown of purines
- Up to 10g/day (kidney normally excretes 500mg/day) due to rapid breakdown of malignant cells; formation of uric acid crystals, obstruction of renal tubules = AKI/hyperuricemia
> AKI = oliguria/anuria (little to no urine)
> Fluid overload = pulmonary oedema
Phosphate
- Large amount in malignant cells
- Renal excretion overloaded (impaired if urate nephrology has caused AKI already) = hyperphosphataemia
Calcium
- Hyperphosphataemia results in hypocalcaemia (forms calcium phosphate crystals)
- Renal excretion overloaded
Potassium
- Lysed cells release large amounts of potassium = hyperkalemia
- Renal excretion overloaded
> Can lead to heart failure
What is the prognosis for TLS?
- Prevention/early intervention important
- Prompt treatment usually successful w/metabolic disturbances
- Resolves within 5-7 days of chemotherapy
What is the prophylactic treatment for high-risk TLS?
- IV fluids; 3L/m^2/day
- Maintain urine output > 100ml/hour
- Rasburicase
- TLS screen; checking U&Es
- Consider delaying chemotherapy for 24-48 hours
What is the prophylactic treatment for moderate risk TLS?
- IV fluids
- Maintain urine output > 100ml/hour
- Allopurinol (NOT Rasburicase)
- TLS screen
What is the prophylactic treatment for low risk TLS?
- Allopurinol (on its own)
What cancers are high, moderate or low risk for TLS?
High:
- Burkitt lymphoma, Burkitt lymphoma type ALL
- ALL (Acute lymphoblastic leukemia), AML (Acute myeloid leukemia)
- WCC > 100 x 10^9/L
Moderate:
- AML w/WCC > 50 x 10^9/L
- Other ALL
- High grade NHL (Non-Hodgkin’s lymphoma) w/bulky disease
Low:
- Other AML
- Myeloma
- CLL (Chronic lymphocytic leukemia)
- Hodgkin Lymphoma
- MDS (Myelodysplastic Syndromes)
What is the treatment strategy for established TLS?
- Vigorous hydration to maintain urine output > 100ml/hour
- Correct hyperkalemia
- Rasburicase
- Seek ICU/renal specialist help; patients may need haemofiltration/haemodialysis (remove electrolytes)
- Only symptomatic hypocalcaemia should be treated
Why is hypocalcaemia only treated in TLS if symptomatic?
- Supplementing calcium could result in calcium phosphate crystal formation (hyperphosphataemia already)
- Insoluble crystals in renal tubules/urine
- More renal damage
What is rasburicase’s mechanism of action?
- Recombinant form of urate oxidase (not found in humans)
- Catalyses the oxidation of uric acid to allantoin
- Allantoin 5 times more soluble; readily excreted
What is the mechanism of action of allopurinol, and why is it not used in conjunction w/rasburicase?
- Blocks conversion of xanthines to uric acid (inhibits xanthine oxidase)
- Reducing effect of rasburicase as a result; conversion of Xanthine to Uric Acid desired so that Rasburicase can convert UA to Allantoin to be readily excreted
- Allantoin more soluble than Xanthine
How is rasburicase given for TLS, and when is it given?
- Give in 50ml 0.9% NaCl over 30 mins (max dose 20 mg)
- First dose PRIOR to starting chemotherapy
What is the pharmacist’s role in TLS treatment?
- Identification of high risk patients
- Ensure allopurinol is stopped in patients due to receive rasburicase
- But also ensure allopurinol is commenced in medium/low risk patients
- Dosing of rasburicase
- Ensure TLS screen completed
- Advice re-electrolyte replacement (e.g. treating hyperkalaemia)
- Restarting allopurinol when rasburicase stopped (the next day)
What is CINV, and why is it an important issue?
- Chemotherapy induced N&V
- CINV is one of the most distressing symptoms; significant impact on QoL
What are the risk factors of CINV?
- < 50 years old
- Female
- Vomiting during previou chemotherapy
- Pregnancy induced N&V (morning sickness etc.)
- History of morning sickness
- LOW ALCOHOL INTAKE (high intake = less susceptible)
What are other causes of N&V as opposed to CINV?
- Radiotherapy (particularly abdomen/brain)
- Brain metastases (increased intracranial pressure)
- Migraine
- UTIs
- Bowel obstruction
- Hypercalcaemia
- Other medications e.g. opioids, antibiotics (erythromycins, macrolides)
What are the types of N&V associated w/chemotherapy?
- Acute vomiting (first 24hrs)
- Delayed N&V (24hrs - 5 days; hard to treat)
- Breakthrough N&V; where normally well controlled but certain things trigger it e.g. warm food, car journey
- Refractory vomiting (when antiemetic ineffective)
- Anticipatory N&V; the thought of chemotherapy, especially if bad experience before
What are the potential consequences of CINV?
- Delayed therapy, omitted doses (PO)
- Dose reductions (want MTD though)
- Dehydration
- Physical damage; oesophageal tears w/violent vomiting
- Electrolyte imbalance
- Increased hospitalization
- Increased institutional costs
- Patient stops treatment completely
What is the treatment of CINV dependent on?
The emetogenicity of the chemotherapy and the type of CINV experienced.
For minimal emetogenicity of chemo regimen, what treatment is given for CINV?
Post chemotherapy:
- Metoclopramide (10mg QDS, PRN orally)
For low emetogenicity of chemo regimen, what treatment is given for CINV?
Pre chemo:
- Metoclopramide 20mg PO (acts on 5-HT3 at higher doses as antagonist as well as DA)
Post chemo:
- Metoclopramide (10mg QDS, PRN orally; as minimal emetogenicity)
For moderate emetogenicity of chemo regimen, what treatment is given for CINV?
Pre chemo:
- Ondansetron 8mg IV/O
- Dexamethasone 8mg IV/O
Post chemo:
- Metoclopramide (10mg QDS for 2 days, then QDS PRN)
- Dexamethasone (2mg BD for 2 days)
For high emetogenicity of chemo regimen, what treatment is given for CINV?
Pre chemo:
- Ondansetron 8mg IV/O
- Dexamethasone 8mg IV/O (as moderate)
Post chemo:
- Metoclopramide (10mg QDS for FOUR (4; instead of 2 in moderate) days, then QDS PRN)
- Dexamethasone (4mg BD for 2 days, then 2mg BD 2 days; taper dose, unlike moderate)
Why is Dexamethasone given for CINV?
- Mode of action not known; thought to act on PGs in the brain
- Has anti-emetic properties for acute and delayed N&V
Which anti-emetics are more effective for acute and delayed N&V respectively?
Acute: metoclopramide
Delayed: ondansetron
What is Aprepitant, and when is it used?
- Neurokinin 1 (NK1) receptor antagonist
- Mediates action of Substance P (emetogenic)
- For use w/platinum based compounds and moderately emetogenic regimens
»> Add-on therapy - Interaction w/dexamethasone (enhances effects, but no dose reduction in practice)
- Dose; 125mg one hour prior to chemotherapy
- 80mg OD on days 2 and 3 (for one day course of chemotherapy)
What does Anticipatory N&V entail, and what is the treatment?
- N&V that can occur prior to a new cycle of chemo
- Usually a result of poor controlled acute and delayed N&V in previous cycles, or in chemotherapy naive patients
»> Sublingual lorazepam 0.5-1mg prior to treatment can help; SL instead of PO as N&V
> Hypnosis, CBT can be helpful
What is the pharmacist’s role in CINV?
- Identification of high risk patients
- Ensuring the appropriate antiemetic regimen regimen has been prescribed
- Counselling patient; Metoclopramide 30 mins - 1 hour before meals
- W/aprepitant; prescribed for next cycle of chemotherapy (patient can take loading dose at home; less waiting around)
- Ensuring antiemetics are stepped up if patient is admitted w/N&V
What is neutropenic sepsis, and how is it defined?
- Whole body reaction triggered by infection (low neutrophil count)
- Patient has recently received cytotoxic chemotherapy AND has had a temperature of 38.5 Degrees on a single occasion, or 38.0 Degrees on two occasions
- Neutropenia; neutrophil count < 1 x 10^9/L
- Treat before FBC results back; can always stop antibiotics if needed (prevent death)
What investigations are undertaken for suspected Neutropenic sepsis?
- FBC (full blood count)
- Blood cultures
- CRP; C-reactive protein, marker for inflammation produced by liver following IL-6 secretion by macrophages/T-cells
- U&Es
- Lactate; how sick is the patient?
What is the treatment for neutropenic sepsis?
Treat the cause of infection:
- Piperacillin/tazobactam (4.5g TDS)
- Add in vancomycin/teicoplanin if patient is known/previously MRSA +ve (or if patient has in-dwelling line, Hickman/Brotac etc anything under skin)
- Gentamicin single dose (5mg/kg)
What is the treatment for neutropenic sepsis in moderate penicillin allergy?
- Meropenem (switch to)
- Add in vancomycin/teicoplanin if patient is known/previously MRSA +ve etc. as before
What is the treatment for neutropenic sepsis in severe penicillin allergy?
- Ciprofloxacin oral/IV (similar bioavailability); but cross-reactivity w/carbapenems + penicillins
- Add in vancomycin/teicoplanin if patient is known/previously MRSA +ve etc. as before
- Gentamicin single dose
What is the pharmacist’s role in neutropenic sepsis treatment?
- Establish nature of any penicillin allergy (what patient classes as an ‘allergy’ may just be mild reaction), advise accordingly
- Ensure door to needle time is < 1 hour (after patient turns up on ward/day care, antibiotics to be given within 1 hour; increased survival)
- Check antibiotic therapy is reviewed regularly; change if necessary, switch to PO where possible.
- Monitor U&Es, FBC, CRP, lactate and vancomycin levels
