Chemotherapy Dosing and Monitoring Flashcards
(46 cards)
1
Q
Why is getting the dose right important?
A
- Too much; kill patient (toxicity)
- Undertreat, patient dies
»> 20% dose reduction may virtually eliminate an otherwise high complete remission rate by as much as 50%.
2
Q
What is the most widely used method of dosing chemotherapy? What does it entail?
A
Body surface area (BSA)
- Based on a patient’s height and weight
- Several formulas, but DuBois and DuBois is most commonly used.
- Patient’s BSA can vary between 1.71 - 1.93 m^2 for the same height and weight w/different formulas.
3
Q
What is the DuBois and DuBois estimation of BSA based on? What were their findings?
A
- Based on measuring surface area of 9 cadavers
- SA = (W^0.425 x H^0.725) x 0.007184
- Demonstrated correlation between blood volume, circulating plasma proteins, renal function and BSA.
4
Q
How accurate is BSA e.g. for cachectic/obese?
A
- BSA can vary in the same way BMI does; people with the same BSA can have v. different builds
5
Q
What is Ideal Body Weight?
A
A weight that is to be healthy for a particular height.
6
Q
When is IBW used over ABW for BSA dosing?
A
- ABW (Actual) used normally; unless patient is obese or cachectic (v. thin)
- Would use IBW for these instances
7
Q
How does treatment intent influence if ABW or IBW is used for BSA dosing?
A
- May use ABW if treatment intent is curative; no evidence that toxicity is increased.
8
Q
What are the issues with capping BSA at 2m^2 (and 2.2m^2 in haematology)?
A
- Risk that obese patients may be undertreated
- Many consultants no longer capping curative regimens; less risk of larger patients relapsing.
9
Q
What are the disadvantages of using BSA to dose chemotherapy?
A
- Does not consider effect of renal disease impairment (even if correlation w/renal function)
- BSA is estimated; not accurate (based on rando cadavers)
- Formulae takes no account of obesity/cachexia
- No direct relationship between BSA dosing and drug clearance
- No direct relationship between BSA dosing and outcome
- Rounding occurs during BSA calculation; introducing even more inaccuracy
10
Q
Why is BSA still used as the standard if there are so many disadvantages?
A
- Continues to be used as original Phase I and II trials used BSA (despite inaccuracies)
- Starting point for dosing, then adjusted after 1st cycle, based on response, toxicity etc. (usually adjusted down due to S/Es)
11
Q
What are the causes of variation with chemotherapy dosing?
A
Individual patient drug handling +/- 15%:
- Pharmacogenetics
- Disease effects
- Hepatic/renal dysfunction
- Co-morbidities
Vial contents +/- 15%:
- Manufacturer may change as hospital looking for cheapest (each one is different)
- Vial type
- Aseptic technique (sharing etc.)
Weight, Height, BSA +/- 10%:
- Shoes
- Clothes
- Time of day (fasting/fed)
- Calibration (scales)
- Method of BSA calculation
Syringe accuracy +/- 5%:
- Manufacturer
- Type
- Size (3ml vs. 50ml)
- Air bubbles etc.
Residual volumes during administration +/- 5%:
- Filter absorption
- Administration set
- Needle
- Practice (inadequate flushing of line after)
12
Q
When is Area Under Curve (AUC) used to dose chemotherapy?
A
- To dose carboplatin (alternative to Cisplatin in pts. w/deteriorating renal function)
- Calculates dose based on creatinine clearance; need accurate GFR
13
Q
What method would you use to calculate GFR to work out AUC dosing?
A
- Cockcroft-Gault
»> eGFR not sufficient; fine for most renally excreted drugs but not for nephrotoxics; based on a 1.73 m^2 BSA
»> eGFR would not be accurate for obese/cachexic patients
14
Q
Cockcroft-Gault (for AUC) requires a body weight; when would you use Ideal Body Weight, Adjusted Body Weight and Actual Body Weight?
A
- Most BSA uses actual body weight
- But, IBW used in nephrotoxic drugs to calculate GFR.
- If actual weight is 30% more than IBW, then used adjusted body weight (v.obese/elderly):
ABW = IBW + 0.4 (actual weight - IBW)
15
Q
In what patients is it ideal to use IBW in calculating nephrotoxic chemotherapy?
A
- Patients < 39 years
- BMI > 30
16
Q
What is the best practice measure of GFR?
A
Using radiolabelled EDTA/DPTA:
- Patients injected with it
- Bloods taken at 2, 3, 4 hours
- Serine blood tests show how quickly isotope is cleared, providing an accurate measure of GFR.
17
Q
In what patients should radiolabelled EDTA be used to calculate GFR (for AUC) prior to carboplatin therapy?
A
- Cachexic
- Obese
- Elderly
- Children
18
Q
When is anticancer therapy dosed by body weight? Advantages?
A
- Mostly biologicals (newer) e.g. bevacizumab, trastuzumab etc
- Doses not capped
- Easier to calculate (less risk of error)
- Uses recent, accurate weight
19
Q
What are the issues with weight-based dosing?
A
- May under-dose with small body size
- May overdose in large body size (BSA may not necessarily be larger)
»> Use IBW or ABW
20
Q
When is fixed dose dosing used? Advantages?
A
- New oral biologicals e.g. TKIs ‘nibs’
- Suitable for drugs w/wide therapeutic window
- Ease of dose preparation
- Reduced cost
- Lower risk of dosing errors
21
Q
What are the issues with fixed dosing?
A
- Overdose small body size
- Underdose large body size
(Opposite of weight based dosing)
22
Q
What does dose banding entail? How are the tables designed?
A
- Individually calculated doses, placed within different bands
- Predetermined starting dose applied to each band
- Tables designed so that maximum variation between standard dose administered to patient and prescribed dose is < 5%
23
Q
What are the different dose banding methods availible?
A
- Linear
- Target
- Logarithmic
24
Q
What does Linear dose banding entail?
A
- BSA centered dose banding
- E.g. Capecitabine tablets only availible as 150mg/500mg, patient w/BSA 1.74 m^2 needs a dose of 1000mg/m^2 BD.
What dose prescribed?
»> 1650mg or 1800mg (+/- 3-5%; prescribed dose of 1740mg)
> 1800 mg prescribed (max for BSA)
25
What does Target dose banding entail?
- Drug centered dose banding, or 'target dose' banding
| - E.g. rituximab is dosed on BSA< then rounded up/down to nearest band
26
What does Logarithmic dose banding entail?
- 80% rule for calculating dose bands, e.g. 100%, 80%, 64%, 51.2% rather than 100/80/80 in linear dose banding.
- Not widely used
27
What are the benefits of dose banding?
- Dose rationalisation/standardising
- Fewer dose calculation errors
- Quicker dispensing through use of pre-prepared doses (pre-prepared syringes/infusions
- Administration of chemotherapy on any chosen day is facilitated
- Rationalisation of demand, with aseptic capacity liberated for more complex chemotherapy and more time for clinical duties
- Reduced waste by re-use of cancelled doses and avoidance of incomplete vial usage during aseptic production
- Use of smaller syringe sizes make bolus administration easier
- Easier processing of dose reductions at short notice
28
What are the disadvantages of using dose banding?
- Administered dose may vary from BSA calculated dose by up to +/- 5% (but BSA not accurate anyway)
- Up to three syringes needed for bolus dose
- Risks associated with manipulation of multiple syringes
- RSI risk for aseptic operators/nurses administering w/repeated syringe manipulation
- Banded doses may be more expensive (acquisition cost) if outsourced
29
What are the potential benefits of TDM?
- Cytotoxic drugs fulfil prerequisites for TDM
- May improve clinical outcome and tolerability
- Identifies patients not adhering to patient
- Allows individual dose optimisation
30
What are the disadvantages of TDM?
- Tumour heterogeneity
- Required drug concentration usually unknown
- Time lag between clinical measurement and effect
- Drugs have overlapping therapeutics and toxic effects
- TDM more complicated in drugs with non-linear kinetics
- Practical or economic considerations; serial samples, training of staff etc.
31
Why is high dose MTX the only cytotoxic where plasma levels are routinely monitored?
- To ensure MTX is being cleared (rather than to check a therapeutic range has been reached)
- Folinic acid given until MTX is < 0.2 micromol/L
32
How does MTX work?
- Folate antagonist (inhibits DHFR)
- THF is active form of folic acid required for purine and thymidylate synthesis; folate acid reduced to THF by DHFR.
- MTX inhibits DHFR.
33
Why is folinic acid (leucovorin) given, 24 hours after MTX?
- 'Rescue' to block unwanted S/Es (damage to healthy tissue)
- Overcomes metabolic blockade caused by MTX
- May block the effects of MTX if given too soon after; as it does not require DHFR for activation.
> Hydrate patient too
> As well as maintaining urine pH > 7 with sodium bicarbonate infusions (prevent crystal formation; COO- salt form in body)
34
Why is chemotherapy given in cycles? When is it appropriate to start the following cycle?
- Scheduling based on effects of cytotoxics on normal and tumour cells
- Rapidly proliferating cells much more sensitive to damage: bone marrow, mucosal epithelial cells of the oropharynx, gut, bladder, hair follicles
- Bone marrow and epithelial lining cells have large capacity for tolerating and recovering from damage
- Normal cells recover from damage within 2-3 weeks; thus successive course given 3 weekly to allow health cells to recover
- Next course not given until damage from previous drug exposure repaired
35
When does maximum damage from cytotoxic chemotherapy occur during a cycle of chemotherapy? When is the WCC nadir?
- Few days-1 week after each treatment
- Nadir WCC: 7-10 days
- Normal cells: recover over 2-3 weeks
36
How are toxicity grades outlined?
Patient is assessed for toxicities before each cycle; scored Grade 1-5.
1) Mild; asymptomatic or mild symptoms, clinical or diagnostic observations only; intervention not required
2) Moderate; minimal, local or non invasive intervention indicated; limiting age-appropriate ADL (activities of daily living)
3) Severe or medically significant but not immediately life-threatening; hospitalization (or prolonged) indicated; disabling; limiting self care ADL
4) Life-threatening consequences; urgent intervention required
5) Death related to Adverse Effects
37
What considerations need to be made re. Renal Function and chemotherapy?
- Nephrotoxic/renally excreted drugs; calculate CrCl or GFR measurement (EDTA)
- Check CrCl prior to each cycle
- Cisplatin; even if renal function okay, patient is pre-hydrated, urine output monitored carefully
> Switch to carboplatin if declining renal function
- Individual SPCs advise dose reduction
38
What is the pre-hydration routine required for Cisplatin treatment?
- Patient gets 1L of saline over 1hr, needs to pass > 100 ml urine.
- If this doesn't happen; 500 ml saline over 30 mins, 100 ml mannitol 10%
- If urine output still not adequate; do chemo another day.
39
How does a patient's Full Blood Count (FBC) influence chemotherapy treatment?
- FBC and differential checked 24 hours prior to next cycle
- Review Hb, Plt, and ANC
- If Hb low = blood transfusion
- If platelets < 30; platelet transfusion (otherwise delay chemo)
- ANC low; delay chemo until > 0.5, 1.0 or 1.5 depending on protocol (consider GCSF; granulocyte-colony stimulating factor with next cycle)
40
What does GCSF do? When and how is GCSF used?
- Granulocyte-colony stimulating factor
- Significant increase in peripheral neutrophil count
- Avoids treatment delay in patients receiving curative chemotherapy (reduce dose instead of adding GCSF in palliation)
- Not administered within 24 hours of chemotherapy; risk of paradoxical myelosuppression
- Commenced after 48 hours
- S/Es; bone pain
- ANC nadir occurs earlier, recovers faster w/GCSF
41
When is liver function monitored w/chemotherapy?
- Hepatotoxic chemo (6 mercaptopurine)
| - Hepatically-cleared chemo (doxorubicin, docetaxel)
42
What needs to be considered re. LFTs and chemotherapy?
- Damage more likely when higher doses used
- Criteria for dose reduction not always clear
- Consider deranged LFTs when treating primary or secondary tumours in liver
- Abnormal LFTs due to tumour; should improve following chemo
43
What are the two classes of cardiotoxicity possibly caused by cytotoxics?
Patients develop heart failure:
- Type 1; irreversible
- Type 2; reversible
44
What does Type 1 cardiotoxicity entail? Risk factors?
Irreversible:
- Caused by anthracyclines (doxorubicin, epirubicin)
Risk factors:
- Female
- Age
- Rapid administration (lower risk to infuse over 2-3 days w/elastomeric device)
- Exceeding cumulative lifetime dose
- Concomitant mediastinal RT
>>> Can occur at any time during treatment.
45
What does Type 2 cardiotoxicity entail? Risk factors?
Reversible:
- Newer agents e.g. Trastuzumab (Herceptin)
- Risk increases when given with concomitant anthracyclines
46
How is cardiotoxicity risk from cytotoxic therapy managed?
- Pre-treatment echocardiogram (ECHO)
- Caution/CI if heart failure (ECHO regularly during treatment)
- Calculate lifetime cumulative dose if relapse
