Carboplatin AUC Calculator [Updated Version- 2017] - GlobalRPH (2024)

Carboplatin AUC Calculator [Updated version- 2017]

Background Info

Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospectiveevaluation of a simple formula based on renal function. J Clin Oncol.1989;7:1748-1756.

AUC = target area under the concentration versus time curvein mg/mL•min.
GFR was measured by 51Cr-EDTA clearance. Estimations of GFRare frequently used in clinical practice, however, several important pointsshould be reviewed (see below).

Relevant package insert data:
Previously treated patients: a target AUC of 4-6 mg/mL•min using singleagent Carboplatin Inj appears to provide the most appropriate dose range.For patients who previously DID NOT receive chemotherapy (untreated), atarget AUC of 7 (range: 6-8) mg/mL per minute has been recommended whencarboplatin is used alone.

Dose Adjustment Recommendations: Pretreatment platelet count and performancestatus are important prognostic factors for severity of myelosuppression inpreviously treated patients. The suggested dose adjustments for single agentor combination therapy shown in the table below are modified from controlledtrials in previously treated and untreated patients with ovarian carcinoma.Blood counts were done weekly, and the recommendations are based on thelowest post-treatment platelet or neutrophil value.

Platelets NeutrophilsAdjusted Dose* (From Prior Course)
>100,000>2000125%
50-100,000 500-2000No Adjustment
<50,000<50075%

Important points

1) The use of the Calvert formula in patients with a GFR or CRCL less than15 to 20 ml/min is not recommended based on insufficent accuracy.
Package insert: The data available for patients with severely impairedkidney function (creatinine clearance below 15 mL/min) are too limited topermit a recommendation for treatment.

2) Fluctuating serum creatinine values DO NOT provide an accurate CrClestimate.

3) GFR estimation: Definitive guidelines or method of determination has notbeen firmly established. Unreliable results may be obtained in patients whoare outside the normal weight range (e.g. obese or cachectic patients).

4) The package insert does not provide a specific formula for GFRestimation.

5) AUC-based carboplatin dosing is more accurate than dosing according toBSA.

6) Several factors must be considered in addition to the GFR to determinethe precise dosage. Additional factors that should be assessed include:previous exposure to chemotherapy or radiotherapy, and overall healthstatus.

References

Carboplatin dosage

Estimated Clearance Equations

Reference:
co*ckcroft DW, Gault MH. Prediction of creatinine clearance fromserum creatinine. Nephron 1976;16(1):31-41.

The original co*ckcroft and Gault equation utilized total body weight,however, the most commonly used version of this equation incorporates theIdeal body weight (IBW) or an adjusted body weight (ABW) in obese patientswhose 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 * (actualbody weight - ideal body weight)]

Alternative equation:
ABW (kg) = ideal body weight + [0.3 * (actualbody weight - ideal body weight)]

Reference:
1) Bauer LA. Applied clinical pharmaco*kinetics. New York: McGraw Hill,Medical Publishing Division; 2001:93-179.
2) Winter, M.E., 2004. Basic pharmaco*kinetics. London: Lippincott Williamsand 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 becollected. 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 ifheight and weight be known. Arch Intern Med. 1916; 17:863–71.

GFR = 141 x min(Scr/κ,1)^α x max(Scr/κ,1)^-1.209x 0.993^Age x 1.018 [iffemale]
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 info for height less than 60 inches

1] Intuitive Method:
Reference: Murdaugh LB. Competence Assessment Tools forHealth-System Pharmacies. 5th ed. Bethesda, MD: ASHP; 2015. [Chap:29 Medicationdosing 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 60inches, the result is reasonable, however, 2.3 kg/inch is excessive whenused for shorter heights. At 38 inches for a male, and 40 inchesfor a female, the IBW is ZERO. This provides support for thenext method below.

2] Baseline Method:
The baseline method starts with the initial ideal body weight baselinevalues 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. Thereforea male patient - 55 inches: IBW = 50kg - (0.833 x 5) = 45.8kg versus thefirst method = 50kg - (2.3 x 5) = 38.5 kg.
[Reference: reasonable assumption based on the standard ideal body weightequations and the baseline weights established for a height of 60 inches.
Also review: Murphy JE. Introduction. In: Murphy JE, ed. Clinical Pharmaco*kinetics, 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 standardIBW equations: Male: 60 inches - 50kg - BMI= 21.53. Female:60 inches - 45.5kg - BMI= 19.59. We can then use this associationto generate an equivalent ideal weight based on this standardized BMIand the height of the patient. Using the example above (55 inchmale 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 aparticular height (units: kg/m²). Example: the followingpatients all have a BMI ~ 21: 130 lbs - 5'6", 163 lbs - 6'2",107 lbs - 5'.

Reference: Hume R. Prediction of lean body mass from height andweight. J Clin Path(1966), 19, 389.

References

1. co*ckcroft DW, Gault MH. Prediction of creatinine clearance from serumcreatinine. Nephron 1976;16(1):31-41
2. Davis GA, Chandler MH. Comparison of creatinine clearance estimationmethods 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. Dettli LC. Drug dosage in patients with renal disease. Clin PharmacolTher 1974;16:274-80.
   
5. Drusano LG, Munice HL, Hoopes JM et al. Commonly used methods ofestimating creatinine clearance are inadequate for elderly debilitatednursing home patients. J Am Geriatrics Soc 1998;36:437-41.
   
6. Hailemeskel B, Namanny M, Kurz A. Estimating aminoglycoside dosagerequirements in patients with low serum creatinine concentrations. Am JHealth-Syst Pharm 1997;54:986-7.
   
7. Jelliffe RW. Estimation of creatinine clearance when urine cannot becollected. Lancet 1971;1:975-6.
8. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease:Evaluation, Classification, and Stratification. © 2002 National KidneyFoundation. (link)
   
9. Levey AS, Greene T, Kusek JW, et al. A simplified equation to predictglomerular filtration rate from serum creatinine (Abstr) J Am Soc Nephrol2000;(11):155A
   
10. Levey AS, Greene T, Schluchter MD, et al. Glomerular filtration ratemeasurements in clinical trials. Modification of Diet in Renal Disease StudyGroup and the Diabetes Control and Complications Trial Research Group. J AmSoc Nephrol 1993;4(5):1159-71
    
11. Levey AS. Assessing the effectiveness of therapy to prevent theprogression of renal disease. Am J Kidney Dis 1993;22(1):207-14
    
12. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimateglomerular filtration rate from serum creatinine: a new prediction equation.Modification of Diet in Renal Disease Study Group. Ann Intern Med1999;130(6):461-70
    
13. 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 NewEquation to Estimate Glomerular Filtration Rate.Ann Intern Med. 2009; 150:604-612.
    
14. Rhodes RS, Sims PJ, Culbertson VL et al. Accuracy of creatinineclearance estimates in geriatric males with elevated serum creatinineclearance. J Geriatric Drug Ther 1991;5:31-45.
    
15. Salazar DE, Corcoran GB: Predicting creatinine clearance and renaldrug clearance in obese patients from estimated fat-free body mass. Am JMed 84: 1053-1060, 1988.
    
16. Smythe M, Hoffman J, Kizy K et al. Estimating creatinine clearance inelderly patients with low serum creatinine concentrations. Am J Hosp Pharm1994;51:189-204.
    
17. Wilhelm SM, Pramodini KP. EstimatingCreatinine Clearance: A Meta-analysis. Pharmacotherapy 2011 31:7 ,658-664.

    "Conclusion.. Using the co*ckcroft-Gault equation with nobody weight (NBW) and actual Scr value most closely estimated measuredClcr. In obese patients, it may be reasonable to use actual body weightwith a correction factor of 0.3 or 0.4 and actual Scr value in theco*ckcroft-Gault equation. Based on this analysis, the use of total bodyweight, ideal body weight, and a rounded Scr value cannot berecommended."

18. Janowitz T, Williams EH, et al. New Model for EstimatingGlomerular Filtration Rate in Patients With Cancer. J Clin Oncol. 2017Jul 7:JCO2017727578.
    https://www.ncbi.nlm.nih.gov/pubmed/28686534
    

    Abstract:
    Purpose
    The glomerular filtration rate (GFR) is essential forcarboplatin chemotherapy dosing; however, the best method toestimate GFR in patients with cancer is unknown. We identifythe most accurate and least biased method.

    Results
    Between August 2006 and January 2013, data from 2,471 patientswere obtained. The new model improved the eGFR accuracy (RMSE,15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with allpublished models. Body surface area (BSA)–adjusted chronickidney disease epidemiology (CKD-EPI) was the most accuratepublished model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to17.38 mL/min) for the internal validation set. Importantly,the new model reduced the fraction of patients with acarboplatin dose absolute percentage error > 20% to 14.17% incontrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% forthe co*ckcroft-Gault formula. The results were externallyvalidated.

    Conclusion
    In a large data set from patients with cancer, BSA-adjustedCKD-EPI is the most accurate published model to predict GFR.The new model improves this estimation and may present a newstandard 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]