Carboplatin AUC Calculator
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New version -
Based on new research (see below), the CKD-EPI equation (corrected for BSA) was added as an
additional clearance equation. A new reporting section was added to the
new program as well. After reviewing several test patients, there is
potential for significant disparity in dosage compared to conventional clearance
equations. In a few test patients the calculated carboplatin dose was
considerably higher with this new method. Our standard
multi-clearance output should help you make an informed decision in determining
an appropriate final carboplatin dose.
Janowitz T, Williams EH, et al. New Model for Estimating
Glomerular Filtration Rate in Patients With Cancer. J Clin Oncol. 2017
Jul 7:JCO2017727578. Dave's Note: an older
study (2012) determined that the CKD-EPI equation had the highest likelihood of
overestimating the dose of carboplatin:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494427/ |
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Age:
Scr:
Gender:
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Height:
Weight:
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Target AUC:
(mg/ml/min) |
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Is this a previously treated patient? :
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Is the serum creatinine (Scr) currently stable:
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Restrict the maximum calculated clearance to this value:
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Select option for calculating the IBW for patients under 60 inches
(default option - BMI method) - ignore for all other patients.:
[See reference section] |
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Background Info
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CALVERT FORMULA FOR CARBOPLATIN DOSING:
Total Dose (mg) = (target AUC) x (GFR + 25)
Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective
evaluation of a simple formula based on renal function. J Clin Oncol.
1989;7:1748-1756.
AUC = target area under the concentration versus time curve
in mg/mL•min.
GFR was measured by 51Cr-EDTA clearance. Estimations of GFR
are frequently used in clinical practice, however, several important points
should be reviewed (see below).
Relevant package insert data:
Previously treated patients: a target AUC of 4-6 mg/mL•min using single
agent Carboplatin Inj appears to provide the most appropriate dose range.
For patients who previously DID NOT receive chemotherapy (untreated), a
target AUC of 7 (range: 6-8) mg/mL per minute has been recommended when
carboplatin is used alone.
Dose Adjustment Recommendations: Pretreatment platelet count and performance
status are important prognostic factors for severity of myelosuppression in
previously treated patients. The suggested dose adjustments for single agent
or combination therapy shown in the table below are modified from controlled
trials in previously treated and untreated patients with ovarian carcinoma.
Blood counts were done weekly, and the recommendations are based on the
lowest post-treatment platelet or neutrophil value.
Platelets
Neutrophils
Adjusted Dose* (From Prior Course)
>100,000
>2000
125%
50-100,000 500-2000
No Adjustment
<50,000
<500
75%
Important points
1) The use of the Calvert formula in patients with a GFR or CRCL less than
15 to 20 ml/min is not recommended based on insufficent accuracy.
Package insert: The data available for patients with severely impaired
kidney function (creatinine clearance below 15 mL/min) are too limited to
permit a recommendation for treatment.
2) Fluctuating serum creatinine values DO NOT provide an accurate CrCl
estimate.
3) GFR estimation: Definitive guidelines or method of determination has not
been firmly established. Unreliable results may be obtained in patients who
are outside the normal weight range (e.g. obese or cachectic patients).
4) The package insert does not provide a specific formula for GFR
estimation.
5) AUC-based carboplatin dosing is more accurate than dosing according to
BSA.
6) Several factors must be considered in addition to the GFR to determine
the precise dosage. Additional factors that should be assessed include:
previous exposure to chemotherapy or radiotherapy, and overall health
status. |
References
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Carboplatin dosage
Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective
evaluation of a simple formula based on renal function. J Clin Oncol.
1989;7:1748-1756.
Estimated Clearance Equations
Cockcroft and Gault equation:
Male: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72)
Female: Multiply above result by 0.85
Reference:
Cockcroft DW, Gault MH. Prediction of creatinine clearance from
serum creatinine. Nephron 1976;16(1):31-41.
The original Cockcroft and Gault equation utilized total body weight,
however, the most commonly used version of this equation incorporates the
Ideal body weight (IBW) or an adjusted body weight (ABW) in obese patients
whose actual weight is significantly greater than their IBW.
Ideal body weight (IBW):
IBW (males) = 50 kg + 2.3 x (height [inches] - 60)
IBW (females) = 45.5 kg + 2.3 x (height [inches] - 60)
Reference:
Devine BJ. Gentamicin therapy. DICP. 1974; 8:650–5.
Adjusted body weight (ABW):
ABW (kg) = ideal body weight + [0.4 * (actual
body weight - ideal body weight)]
Alternative equation:
ABW (kg) = ideal body weight + [0.3 * (actual
body weight - ideal body weight)]
Reference:
1) Bauer LA. Applied clinical pharmacokinetics. New York: McGraw Hill,
Medical Publishing Division; 2001:93-179.
2) Winter, M.E., 2004. Basic pharmacokinetics. London: Lippincott Williams
and Williams.
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Jelliffe equation:
Male: (98 - (0.8 * (age - 20)) / (SCR in mg/dL)) x Patient’s BSA/1.73 M2
Female: Multiply above result by 0.9
References:
Jelliffe RW. Estimation of creatinine clearance when urine cannot be
collected. Lancet 1971;1:975-6.
Jelliffe RW. Creatinine clearance: Bedside estimate. Ann Inter Med. 1973;
79:604.
Body Surface Area:
Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if
height and weight be known. Arch Intern Med. 1916; 17:863–71. |
Background info for height less than 60 inches
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If the actual body
weight is less than any of the calculation methods, the actual body
weight will be used.
Discussion of the various methods: The
output of this section is based on research I had completed ~20 years
ago on this subject. A quick review of the recent literature has
not changed or added any new methods for estimating an ideal body weight
for patients less than 60 inches tall. Note: naming convention is
based on my earlier work...
1] Intuitive Method:
Reference: Murdaugh LB. Competence Assessment Tools for
Health-System Pharmacies. 5th ed. Bethesda, MD: ASHP; 2015. [Chap:29 Medication
dosing in Patients with Renal Dysfunction]
IBW (Male) = 50kg - 2.3kg for each inch below 60 inches
IBW (Female) = 45.5kg - 2.3kg for each inch below 60 inches
Comments: For patients just a few inches below 60
inches, the result is reasonable, however, 2.3 kg/inch is excessive when
used for shorter heights. At 38 inches for a male, and 40 inches
for a female, the IBW is ZERO. This provides support for the
next method below.
2] Baseline Method:
The baseline method starts with the initial ideal body weight baseline
values e.g. 60 inch male patient - 50kg and 60 inch female patient -
45.5kg. Male patient: 50kg /60 inches = 0.833 kg/inch.
Female patient = 45.5kg/60 inches = 0.758 kg/inch. Therefore
a male patient - 55 inches: IBW = 50kg - (0.833 x 5) = 45.8kg versus the
first method = 50kg - (2.3 x 5) = 38.5 kg.
[Reference: reasonable assumption based on the standard ideal body weight
equations and the baseline weights established for a height of 60 inches.
Also review: Murphy JE. Introduction. In: Murphy JE, ed. Clinical Pharmacokinetics, 5th ed. Bethesda, MD: American Society of Health-System Pharmacists, 2011:xxxiv.
- Note: for patients who are less than 60 inches tall, the weight should be decreased more conservatively than 2.3kg/inch.]
3] BMI method:
References:
Wiggins, K. L. (2004). Renal care: Resources and practical applications.
Chicago: American Dietetic Association. pg 12.
Barash, P. G., Cullen, B. F., & Stoelting, R. K. (1989). Clinical anesthesia.
Philadelphia: Lippincott. chap:47:1231
Remember that BMI = weight(kg)/height2 (meters squared).
Next, we will establish an 'ideal' BMI based on values in the standard
IBW equations: Male: 60 inches - 50kg - BMI= 21.53. Female:
60 inches - 45.5kg - BMI= 19.59. We can then use this association
to generate an equivalent ideal weight based on this standardized BMI
and the height of the patient. Using the example above (55 inch
male patient):
IBW = 21.53 (BMI value above) x (55 x 0.0254)2 =
42 kg.
Background info: the body mass index quantifies the amount of tissue mass at a
particular height (units: kg/m2). Example: the following
patients all have a BMI ~ 21: 130 lbs - 5'6", 163 lbs - 6'2",
107 lbs - 5'.
BMI
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19
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20
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21
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Height
(inches) |
Body
Weight (pounds) |
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58 |
91 |
96 |
100 |
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59 |
94 |
99 |
104 |
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60 |
97 |
102 |
107 |
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61 |
100 |
106 |
111 |
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62 |
104 |
109 |
115 |
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63 |
107 |
113 |
118 |
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64 |
110 |
116 |
122 |
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65 |
114 |
120 |
126 |
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66 |
118 |
124 |
130 |
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67 |
121 |
127 |
134 |
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68 |
125 |
131 |
138 |
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69 |
128 |
135 |
142 |
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70 |
132 |
139 |
146 |
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71 |
136 |
143 |
150 |
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72 |
140 |
147 |
154 |
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73 |
144 |
151 |
159 |
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74 |
148 |
155 |
163 |
4] Hume method:
LBW (Males) = (0.3281 x Weight in kg) + (0.33939 x Height in cm) -
29.5336
LBW (Females) = (0.29569 x Weight in kg) + (0.41813 x Height in cm) -
43.2933
Using the example above: (55 inch male patient): IBW=
36.9 kg
Reference: Hume R. Prediction of lean body mass from height and
weight. J Clin Path(1966), 19, 389.
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