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B33CAN - Professionalism & Leadership; Clinical & Pharmacy Practice > Chemotherapy Dosing and Monitoring > Flashcards

Chemotherapy Dosing and Monitoring Flashcards

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%.
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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.
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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.
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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
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5
Q

What is Ideal Body Weight?

A

A weight that is to be healthy for a particular height.

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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
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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.
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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.

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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
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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)
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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)
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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
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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
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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)
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15
Q

In what patients is it ideal to use IBW in calculating nephrotoxic chemotherapy?

A
  • Patients < 39 years

- BMI > 30

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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.
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17
Q

In what patients should radiolabelled EDTA be used to calculate GFR (for AUC) prior to carboplatin therapy?

A
  • Cachexic
  • Obese
  • Elderly
  • Children
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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
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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
Q

What does Target dose banding entail?

A
  • Drug centered dose banding, or ‘target dose’ banding

- E.g. rituximab is dosed on BSA< then rounded up/down to nearest band

26
Q

What does Logarithmic dose banding entail?

A
  • 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
Q

What are the benefits of dose banding?

A
  • 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
Q

What are the disadvantages of using dose banding?

A
  • 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
Q

What are the potential benefits of TDM?

A
  • Cytotoxic drugs fulfil prerequisites for TDM
  • May improve clinical outcome and tolerability
  • Identifies patients not adhering to patient
  • Allows individual dose optimisation
30
Q

What are the disadvantages of TDM?

A
  • 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
Q

Why is high dose MTX the only cytotoxic where plasma levels are routinely monitored?

A
  • 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
Q

How does MTX work?

A
  • 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
Q

Why is folinic acid (leucovorin) given, 24 hours after MTX?

A
  • ‘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
Q

Why is chemotherapy given in cycles? When is it appropriate to start the following cycle?

A
  • 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
Q

When does maximum damage from cytotoxic chemotherapy occur during a cycle of chemotherapy? When is the WCC nadir?

A
  • Few days-1 week after each treatment
  • Nadir WCC: 7-10 days
  • Normal cells: recover over 2-3 weeks
36
Q

How are toxicity grades outlined?

A

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
Q

What considerations need to be made re. Renal Function and chemotherapy?

A
  • 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
Q

What is the pre-hydration routine required for Cisplatin treatment?

A
  • 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
Q

How does a patient’s Full Blood Count (FBC) influence chemotherapy treatment?

A
  • 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
Q

What does GCSF do? When and how is GCSF used?

A
  • 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
Q

When is liver function monitored w/chemotherapy?

A
  • Hepatotoxic chemo (6 mercaptopurine)

- Hepatically-cleared chemo (doxorubicin, docetaxel)

42
Q

What needs to be considered re. LFTs and chemotherapy?

A
  • 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
Q

What are the two classes of cardiotoxicity possibly caused by cytotoxics?

A

Patients develop heart failure:

  • Type 1; irreversible
  • Type 2; reversible
44
Q

What does Type 1 cardiotoxicity entail? Risk factors?

A

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
Q

What does Type 2 cardiotoxicity entail? Risk factors?

A

Reversible:
- Newer agents e.g. Trastuzumab (Herceptin)

  • Risk increases when given with concomitant anthracyclines
46
Q

How is cardiotoxicity risk from cytotoxic therapy managed?

A
  • Pre-treatment echocardiogram (ECHO)
  • Caution/CI if heart failure (ECHO regularly during treatment)
  • Calculate lifetime cumulative dose if relapse

B33CAN - Professionalism & Leadership; Clinical & Pharmacy Practice (8 decks)

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