Carboplatin AUC Calculator [Updated version- 2017]
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Based on new research, the CKD-EPI equation (corrected for BSA) was added as an
additional clearance equation. A new reporting section was added as well to the
results section.
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Age:
Scr:
Gender:
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Height:
Weight:
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Target AUC:
(mg/ml/min) |
Is this a previously treated patient? :
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Is the serum creatinine (Scr) currently stable:
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For the CKD-EPI equation. specify race:
[New research18]
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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.
=================
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.
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CKD-EPI equation |
GFR = 141 x min(Scr/κ,1)α x max(Scr/κ,1)-1.209
x 0.993Age x 1.018 [if
female]
x 1.159 [if black]
κ = 0.7 if female.
κ = 0.9 if male.
α = -0.329 if female
α = -0.411 if male
min = the minimum of Scr/κ or 1
max = the maximum of Scr/κ or 1
"BACKGROUND: Equations to estimate glomerular filtration
rate (GFR) are routinely used to assess kidney function. Current
equations have limited precision and systematically underestimate
measured GFR at higher values." 13
"CONCLUSION: The CKD-EPI creatinine equation is more accurate than
the Modification of Diet in Renal Disease Study equation and could
replace it for routine clinical use." 13
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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) |
58 |
91 |
96 |
100 |
59 |
94 |
99 |
104 |
60 |
97 |
102 |
107 |
61 |
100 |
106 |
111 |
62 |
104 |
109 |
115 |
63 |
107 |
113 |
118 |
64 |
110 |
116 |
122 |
65 |
114 |
120 |
126 |
66 |
118 |
124 |
130 |
67 |
121 |
127 |
134 |
68 |
125 |
131 |
138 |
69 |
128 |
135 |
142 |
70 |
132 |
139 |
146 |
71 |
136 |
143 |
150 |
72 |
140 |
147 |
154 |
73 |
144 |
151 |
159 |
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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References
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- Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum
creatinine. Nephron 1976;16(1):31-41
- Davis GA, Chandler MH. Comparison of creatinine clearance estimation
methods in patients with trauma. Am J Health-Syst Pharm 1996;53:1028-32.
- Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics. 2nd ed.
Norwalk, CT: Appleton & Lange; 1994.
- Dettli LC. Drug dosage in patients with renal disease. Clin Pharmacol
Ther 1974;16:274-80.
- Drusano LG, Munice HL, Hoopes JM et al. Commonly used methods of
estimating creatinine clearance are inadequate for elderly debilitated
nursing home patients. J Am Geriatrics Soc 1998;36:437-41.
- Hailemeskel B, Namanny M, Kurz A. Estimating aminoglycoside dosage
requirements in patients with low serum creatinine concentrations. Am J
Health-Syst Pharm 1997;54:986-7.
- Jelliffe RW. Estimation of creatinine clearance when urine cannot be
collected. Lancet 1971;1:975-6.
- KDOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, Classification, and Stratification. © 2002 National Kidney
Foundation. (link)
- Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict
glomerular filtration rate from serum creatinine (Abstr) J Am Soc Nephrol
2000;(11):155A
- Levey AS, Greene T, Schluchter MD, et al. Glomerular filtration rate
measurements in clinical trials. Modification of Diet in Renal Disease Study
Group and the Diabetes Control and Complications Trial Research Group. J Am
Soc Nephrol 1993;4(5):1159-71
- Levey AS. Assessing the effectiveness of therapy to prevent the
progression of renal disease. Am J Kidney Dis 1993;22(1):207-14
- Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate
glomerular filtration rate from serum creatinine: a new prediction equation.
Modification of Diet in Renal Disease Study Group. Ann Intern Med
1999;130(6):461-70
- Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI,
Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A New
Equation to Estimate Glomerular Filtration Rate.
Ann Intern Med. 2009; 150:604-612.
- Rhodes RS, Sims PJ, Culbertson VL et al. Accuracy of creatinine
clearance estimates in geriatric males with elevated serum creatinine
clearance. J Geriatric Drug Ther 1991;5:31-45.
- Salazar DE, Corcoran GB: Predicting creatinine clearance and renal
drug clearance in obese patients from estimated fat-free body mass. Am J
Med 84: 1053-1060, 1988.
- Smythe M, Hoffman J, Kizy K et al. Estimating creatinine clearance in
elderly patients with low serum creatinine concentrations. Am J Hosp Pharm
1994;51:189-204.
- Wilhelm SM, Pramodini KP. Estimating
Creatinine Clearance: A Meta-analysis. Pharmacotherapy 2011 31:7 ,
658-664.
"Conclusion.. Using the Cockcroft-Gault equation with no
body weight (NBW) and actual Scr value most closely estimated measured
Clcr. In obese patients, it may be reasonable to use actual body weight
with a correction factor of 0.3 or 0.4 and actual Scr value in the
Cockcroft-Gault equation. Based on this analysis, the use of total body
weight, ideal body weight, and a rounded Scr value cannot be
recommended." |
- Janowitz T, Williams EH, et al. New Model for Estimating
Glomerular Filtration Rate in Patients With Cancer. J Clin Oncol. 2017
Jul 7:JCO2017727578.
https://www.ncbi.nlm.nih.gov/pubmed/28686534
Abstract:
Purpose
The glomerular filtration rate (GFR) is essential for
carboplatin chemotherapy dosing; however, the best method to
estimate GFR in patients with cancer is unknown. We identify
the most accurate and least biased method.
Results
Between August 2006 and January 2013, data from 2,471 patients
were obtained. The new model improved the eGFR accuracy (RMSE,
15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all
published models. Body surface area (BSA)–adjusted chronic
kidney disease epidemiology (CKD-EPI) was the most accurate
published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to
17.38 mL/min) for the internal validation set. Importantly,
the new model reduced the fraction of patients with a
carboplatin dose absolute percentage error > 20% to 14.17% in
contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for
the Cockcroft-Gault formula. The results were externally
validated.
Conclusion
In a large data set from patients with cancer, BSA-adjusted
CKD-EPI is the most accurate published model to predict GFR.
The new model improves this estimation and may present a new
standard of care.
[Note: GFR equations must be converted to a clearance value -
e.g. ml/min/1.73 m2 x BSA/1.73 = mL/min] |
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