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Carboplatin AUC Calculator

led  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/
Age:    Scr:     Gender:
Height     Weight:
Target AUC  (mg/ml/min)
Is this a previously treated patient? :
Is the serum creatinine (Scr) currently stable:  
Restrict the maximum calculated clearance to this value
Select option for calculating the IBW for patients under 60 inches
(default option - BMI method) - ignore for all other patients.

   [See reference section]

Background Info

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) Flucuating 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

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.

Background info for height less than 60 inches top of page

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

19

20

21

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.

Disclaimer

The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user’s use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Read the disclaimer