Carboplatin AUC Calculator - GlobalRPH Multiple Clearance Analysis

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Carboplatin AUC Calculator

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.

Age: Scr: mg/dL umol/L Gender: Male Female

Height: Inches Centimeters Weight: Kilograms Pounds

Target AUC: (mg/ml/min)

Is this a previously treated patient? : Yes No

Is the serum creatinine (Scr) currently stable: Yes No

Restrict the maximum calculated clearance to this value: 100 ml/min 125 ml/min 150 ml/min DO NOT PLACE LIMITS

Select option for calculating the IBW for patients under 60 inches (default option - BMI method) - ignore for all other patients.: Intuitive Method Baseline Method BMI Method Hume Method [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.

Background info for height less than 60 inches

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.

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Carboplatin AUC Calculator - GlobalRPH Multiple Clearance Analysis