Download CG vs. MDRD

Whitney Jones, PharmD Candidate1; LeAnn B. Norris, PharmD, BCPS2; P. Brandon
Bookstaver, PharmD, BCPS2; Richard Schulz, PhD2
1University
of South Carolina College of Pharmacy, Columbia, SC; 2South Carolina College of Pharmacy,
USC Campus, Columbia, SC
 Carboplatin is a second generation platinum agent
 Used in the treatment of NSCLC
 70% is excreted in the urine
 The Calvert equation
 Carboplatin dose = AUC (GFR+25)
 Standard method for carboplatin dose
calculation1,2
 Correlation between renal clearance and glomerular
filtration rate (GFR)3,4
1Calvert
AH, et al. Clin Oncol 1989;7:1748-56.
SB, et al. Clin Pharmacokinet 1997; 33(3): 161-83.
3Calvert AH, et al. Cancer Chemother Pharmacol 1982; 9: 140-7.
4Herrington JD, et al. Cancer Chemother Pharmacol 2006;57:241-7.
2Duffull
5Ando

C-G equation (original)
 Commonly used in the Calvert formula
 Inaccuracies in carboplatin dosing5

MDRD equation
 More accurate than the C-G equation (GFR < 60 ml/min)
 Sparse data is available in cancer patients and drug dosing6

Modified C-G (mC-G) equation
 Greater accuracy with CrCl < 50 mL/min and BMI < 257
 Improves upon bias and precision of C-G equation8
Y, et al. Br J Cancer 1997;76:1067.
JG, et al. Br J Cancer 2001;84(4):452-9.
7Shoker A, et al. Clin Nephrol 2006;66(2):89-97.
8Rostoker G, et al. J Nephrol 2007;20:576-85.
6Wright

Original C-G (C-G), ml/min
 CrCl = (140-age) x IBW / SCr x 72 (0.85 female)

6-variable MDRD formula, ml/min
 GFR/1.73m2 = 170 x (SCr -0.999) x (Age -0.176) x
(0.762 female) x (1.180 A.A.) x (BUN -0.170) x
(Alb.318)

Modified C-G (mC-G), ml/min
 CrCl/1.73m2 = (140-age) x TBW / SCr x 72 (0.85
female)
 To determine whether a significant difference
exists in comparison of renal function and
carboplatin dosing using the original C-G, mCG, and 6-variable MDRD formulas in a
population of patients treated for non-small
cell lung cancer.

Retrospective, non-interventional study

Conducted at a Veterans Administration Hospital (Columbia,
SC)

Inclusion Criteria:
 Age > 18 years
 Completion of at least one dose of carboplatin

Exclusion Criteria:
 Any diagnosis other than NSCLC
 Albumin measurement > 1 month from first carboplatin
dose

Patients were not duplicated in this study

Primary endpoints:
1. Difference in estimate renal function (CrCl or
GFR) between 3 study formulas
2. Difference in calculated carboplatin doses using
renal function estimates of 3 study formulas

Paired Student t tests were performed

Intra-patient variability measured as clinical
significance, defined as ≥ 20% difference

Accuracy defined as +/- 30% difference in
renal estimation (compared to C-G)
Table 1
Demographics
Gender
Male
Female
Race
Non-African American
African American
Characteristic
Age, years
TBW, kg
BSA, m2
SCr, mg/dL
Albumin, g/dL
n = 128
125
3
79
49
Mean (+/-SD)
62.99 +/- 9.12
78.88 +/- 20.93
1.96 +/- 0.28
1 +/- 0.30
3.2 +/- 0.55
Evaluation of Carboplatin Clearance Calculations
Mean Diff
C-G v. mC-G
5.83
C-G v. MDRD
4.73
mC-G v. MDRD -1.09
SD
12.58
24.13
25.91
95% CI
3.63 – 8.03
0.511 – 8.95
-5.63 – 3.44
P-value
<0.001
0.028
0.634
Evaluation of Carboplatin Dose Calculations
Mean Diff.
C-G v. mC-G
6.05
C-G v. MDRD
7.64
mC-G v. MDRD 1.59
SD
109.6
183.46
131.79
95% CI
-13.12 – 25.22
-24.45 – 39.73
-21.47 – 24.64
P-value
0.533
0.648
0.892

Clinical significance
 Discordance in 14.84% of doses when comparing
C-G to mC-G
 Discordance in 46.09% of doses when comparing
C-G to MDRD
Accuracy (30%) of Renal Estimations
C-G vs. mC-G
C-G vs. MDRD
Number
3
32
% Achievement
3.13
25

Differences exist between the C-G, mC-G, and 6variable MDRD formulas

Application of individual formulas could result in
clinically significant carboplatin dosing modifications

A prospective, controlled study would aid in
determining the optimal formula for renal function
estimations in carboplatin dosing
 Investigation of patient populations

Correlation of carboplatin levels and renal function
prediction