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B33CAN > Chemotherapy Dosing and Monitoring (Tom Gray) > Flashcards

Chemotherapy Dosing and Monitoring (Tom Gray) Flashcards

1
Q

What is the most widely used method of calculating chemotherapy dosing?

A

Body surface area (BSA)

An individual calculation based on height and weight og each patient.

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2
Q

What formulas are used to calculate BSA?

A

Dubois and Dubois

SA = (W0.424 x H0.725 x 71.88) / 10,000 (numbers for W and H to the power).

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3
Q

Where does the Dubois and Dubois formula come from?

A

Wrapped 9 cadavers in bandages and paste to determine surface area.

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4
Q

What is their a correlation between with BSA?

A

Correlation with BSA and renal function.

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5
Q

What is ideal BSA?

A

A healthy ideal BSA for that body type

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6
Q

What is actual BSA?

A

The calculated/ measured BSA.

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7
Q

Is the ideal or actual BSA used when treating/managing patients?

A

Actual

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8
Q

What is the problem with capping BSA?

A

Obese patients may be undertreated if BSA is capped.

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9
Q

What else is considered when managing a dose, alongside BSA?

A

The treatment intent; in curative treatment the dose may be increased because greater side effects are tolerated in the event of cure, this increase also reduces the chances of relapse also.

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10
Q

What are the disadvantages to BSA?

A

BSA is estimated using the Dubois and Dubois numbers.
The effect of renal disease or impairment could be overlooked.
BSA formulae does not consider obesity or cachexia (low body weight as a result of course of the cancer.
There is no precise correlation between dosing and clearance rate.
No direct relationship is shown with BSA and outcome.
Rounding of the BSA calculation and dose usually occurs to give a convenient and measurable dose.

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11
Q

When is BSA used?

A

In clinical trials, Phase I and II continued use.

Used as a starting point for dosing and then adjusted after the first cycle of chemo according to toxicity and response.

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12
Q

What are some of the causes of variation in doses received by patients?

A

Individual patient drug handling; pharmacogenetics, disease effects, renal/hepatic dysfunction, co-morbities.
Vial contents; manufacture variation, vial type, vial sharing.
Weight height BSA; Shoes, clothes, time of day
Syringe accuracy; manufacturer, type, size, use i.e air bubbles etc
Residual volumes during administration; filter, adsorption, practice, flushing of the line.

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13
Q

When is Area Under the Curve used in dosing?

A

AUC used to dose carboplatin (which is renally excreted).

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14
Q

How is AUC calculated?

A

The Calvert equation is used to calculate the dose based on creatinine clearance;

Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25]
GFR comes from Cockroft Gault equation.

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15
Q

When using the Calvert equation what must be considered? (Part of the equation when calculating AUC)

A

The GFR is important and must be accurate
Is the CG equation enough, should calculated GFR be used or should it be measured?
Is it based on actual, ideal or adjusted body weight?

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16
Q

How is the GFR calculated (in general and also for the Calvert equation)?

A

Use ideal body weight (can be an estimate H-100 for men, H-105 for women). CrCl is 46ml/min.
Using adjusted body weight is 53ml/min. Lots of variation.
In reality, never use an estimated GFR

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17
Q

How can GFR be determined without guessing?

A

Radiolabelled EDTA or DPTA is best practice

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18
Q

Which group of drugs are normally dosed based on weight?

A

Biologicals e.g. bevacizumab, trastuzumab, pertuzumab
Generally doses are not capped.
Easier to calculate, use a recent, accurate weight.

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19
Q

What is a problem with dosing based on weight?

A

In low weight patients, may underdose.

In large body sizes, may overdose. The body surface area is not necessarily bigger because they weigh more.

20
Q

When is a fixed dose used? When is this suitable?

A

In new oral biologicals i.e. TKIs “nibs”.

When the drug has a wide therapeutic window

21
Q

What are the benefits of a fixed dose?

A

Ease of dose preparation
Reduced cost
Lower risk of dosing errors

22
Q

What are the problems that can arise from fixed doses?

A

May overdose in small body size patients, may underdose those with a large body size.

23
Q

What is dose banding?

A

Individually calculated doses are placed within defined bands. A predetermined standard dose is applied to each band. Tables are designed so that variation between doses is <5%.

  1. 38 - 1.47
  2. 48-1.57 example intervals
24
Q

Which three dose banding methods are used?

A

Linear, target, logarithmic

25
Q

What is linear dose banding?

A

BSA centered e.g. capecitabine as tabs only available as 150mg / 500mg

26
Q

What is target dose banding?

A

Drug centered approach “target dose” banding.
e.g. Rituximab is dosed based on BSA then rounded up or down to the nearest band. BSA x rituximab/m squared then dose rounded to nearest administerable amount.

27
Q

What is logarithmic dose banding?

A

Uses the 80% rule; for calculating dose bands e.g. 100%, 80%, 64% 51.2% rather than 100% 60% 40% seen in linear dosing.

28
Q

What are the benefits of dose banding?

A

Dose rationalisation
Fewer calculation errors
Quicker dispensing through use of pre-prepared doses
Administration of chemotherapy on any chosen day is facilitated
Reduced patient waiting times
Aseptic capacity liberated for more complex chemotherapy and more time for clinical duties
Reduced wastage by re-use of cancelled doses and avoidance of incomplete vial usage during aseptic production.
Use of smaller syringe sixes making bolus administration easier
Easier processing of dose reductions at short notice.

29
Q

What are the disadvantages to dose banding?

A

The administered dose may vary by up to 5% from the BSA calculated dose.
Up to three syringes may be needed for each bolus dose
Risks associated with multiple syringe manipulation.
RS disorder in workers who have to fill, administer multiple syringes
Banded doses may be more expensive (acquisition cost) if out sourced.

30
Q

What are the potential benefits to therapeutic drug monitoring (TDM)?

A

Cytotoxic drugs fulfil prerequisites for TDM
May improve clinical outcome and tolerability
Identifies patients that are no adhering to treatment. Allows individual dose optimisation.

31
Q

What are the disadvantages to therapeutic drug monitoring (TDM)?

A

Tumour heterogenity
Required drug concentration usually not known
Time lag between clinical measurement and effect
Drugs have overlapping therapeutic and toxic effects
TDM is more complicated in drugs with non-linear kinetics. Practical or economic considerations.

32
Q

Which cytotoxic drug has its plasma levels routinely monitored?

A 
High dose methotrexate
Folate antagonist (inhibits DHFR) 
Used to treat Non-Hodgkin's lymphoma
33
Q

What is the role of folic acid?

A

Folinic acid ‘rescue’ is commneced 24 hours after MTX to block unwanted side-effects (damage to healthy tissue).
Folinic acid is continued until MTX level is <0.2 micromol/L.

34
Q

What is chemotherapy scheduling based on?

A

Based on effects of cytotoxic drug on normal tissue and tumour cells.

35
Q

Which cells are more sensitive to chemotherapy?

A

Rapidly dividing cells are more sensitive to damage

- bone marrow, mucosal epithelial cells, hair follicles

36
Q

How long does it take normal cells to recover from a cycle of chemotherapy?

A

2-3 weeks

On this basis, chemo is given on 3 weekly cycles to allow time for healthy cells to recover.

37
Q

What is the Nadia?

A

When bone marrow is at its lowest point post chemo, 7-10 days

38
Q

Which drugs are adjusted depending on renal function?

A

Nephrotoxic or renally cleared drugs
Calculated CrCl or GFR measurement (EDTA or DTPA)
Check calculated CrCl level prior to each cycle.

39
Q

Which drug is given specific renal care too?

A

Cisplatin
Even if a patients renal function is maximum, they are still pre-hydrated and urine output is monitored regularly and carefully.
If renal function shows decline, may switch to carboplatin.

40
Q

When is a full blood count carried out?

A

FBC checked 24H prior to next cycle.
Review Hb, Plt and absolute neutrophil count (ANC)
If Hb is low - blood transfusion
If platelets are <30 then platelet transfusion, otherwise delate chemotherapy.
ANC low, delay chemo until recovered >0.5, 1.0 or 1.5 depending on protocol. Consider GCSF with next cycle

41
Q

What is GCSF?

A

Granulocyte colony stimulating factor.
When administered it results in significant increase in peripheral neutrophil count.
Used to avoid tratement delay in patients recieving curative chemotherapy.
Do not administer within 24h of chemotherapy, risk of paradoxical myelosuppression.
Main side effect is bone pain.

42
Q

When is it important to monitor liver function?

A

Need to monitor LFTs in patients receiving:
Hepatotoxic chemo, hepatically cleared chemo
* Consider deranged LFTs when treating primary or secondary tumour in the liver.
There is unclear criteria on when to adjust / reduce / stop dose.

43
Q

When is liver damage most likely?

A

When doses are high

44
Q

Which two classes of cardiotoxicity are there in chemotherapy?

A

Type I - irreversible

Type II - reversible

45
Q

Which drugs can cause Type I (irreversible) cardiotoxicity?

A

Anthracycline antibiotics
Risk factors:
Female, age, rapid administration, exceeding cumulative lifetime dose, concomitant mediastinal radiotherapy.
May occur at any time in treatment

46
Q

Which drugs can cause Type II (irreversible) cardiotoxicity?

A

Trastuzumab (newer agents)
Risk increases when given concomitantly with anthracyclines
Both agents are used to treat breast cancer

47
Q

What is the role of a pre-treatment echocardiogram?

A

ECHO needed before drugs with cardiotoxicity
Need ECHO regularly during treatment for monitoring
Lifetime cumulative dose needs calculating if relapse

B33CAN (25 decks)

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