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Carboplatin AUC Calculator [Updated version]

Carboplatin AUC Calculator [Updated version]
Based on new research, the CKD-EPI equation was added as an additional clearance equation.   A new reporting section was added as well to the results section. Our standard multi-clearance output should help you make an informed decision in determining an appropriate final carboplatin dose. Updates 2022-2024 (YouTube)
Age:    Scr:     Gender:
Height:      Weight:
Target AUC:    (mg/ml/min)
Is this a previously treated patient? :
Is the serum creatinine (Scr) currently stable:  

For the CKD-EPI equation (2012). specify race:


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) 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

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.
CKD-EPI equation 2012

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


CKD-EPI Creatinine Equation (2021)

eGFRcr = 142 x min(Scr/κ, 1)α x max(Scr/κ, 1)-1.200 x 0.9938Age x 1.012 [if female]

-----
Scr = standardized serum creatinine in mg/dL
κ = 0.7 (females) or 0.9 (males)
α = -0.241 (female) or -0.302 (male)
min = the minimum of Scr/κ or 1
max =  the maximum of Scr/κ or 1
Age (years)

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.

References
  1.  Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41
  2. DDavis GA, Chandler MH. Comparison of creatinine clearance estimation methods in patients with trauma. Am J Health-Syst Pharm 1996;53:1028-32.
  3. Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics. 2nd ed. Norwalk, CT: Appleton & Lange; 1994.
  4. Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis. 2021;78(1):103-115.
  5. Dettli LC. Drug dosage in patients with renal disease. Clin Pharmacol Ther 1974;16:274-80.
  6. 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.
  7. 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.
  8. Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C–based equations to estimate GFR without race. N Engl J Med. 2021;385:1737-1749.
  9. Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971;1:975-6.
  10. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. © 2002 National Kidney Foundation. (link)
  11. Kidney.org. CKD-EPI Creatinine Equation (2021).
  12. 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
  13. 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
  14. Levey AS. Assessing the effectiveness of therapy to prevent the progression of renal disease. Am J Kidney Dis 1993;22(1):207-14
  15. 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
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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."
  21. 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]
Carboplatin AUC Calculator [Updated version]

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