1. Evaluation of the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (C-G) formulas in the Calvert equation for Carboplatin Dosing
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

2. Background 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: Duffull SB, et al. Clin Pharmacokinet 1997; 33(3): Calvert AH, et al. Cancer Chemother Pharmacol 1982; 9: Herrington JD, et al. Cancer Chemother Pharmacol 2006;57:241-7.

3. Background 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
5Ando Y, et al. Br J Cancer 1997;76: Wright JG, et al. Br J Cancer 2001;84(4): Shoker A, et al. Clin Nephrol 2006;66(2): Rostoker G, et al. J Nephrol 2007;20:

4. Renal Clearance Equations
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 ) x (Age ) x (0.762 female) x (1.180 A.A.) x (BUN ) x (Alb.318)
Modified C-G (mC-G), ml/min
CrCl/1.73m2 = (140-age) x TBW / SCr x 72 (0.85 female)

5. Study Objective
To determine whether a significant difference exists in comparison of renal function and carboplatin dosing using the original C-G, mC-G, and 6-variable MDRD formulas in a population of patients treated for non-small cell lung cancer.

6. Methods 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

7. Endpoints Primary endpoints:
Difference in estimate renal function (CrCl or GFR) between 3 study formulas
Difference in calculated carboplatin doses using renal function estimates of 3 study formulas

8. Analysis 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)

9. Results Table 1 Demographics n = 128 Gender Male 125 Female 3 Race
Non-African American 79
African American
Characteristic Mean (+/-SD)
Age, years /- 9.12
TBW, kg /
BSA, m /- 0.28
SCr, mg/dL /- 0.30
Albumin, g/dL /- 0.55

10. Results Evaluation of Carboplatin Clearance Calculations
Mean Diff SD % CI P-value
C-G v. mC-G – <0.001
C-G v. MDRD –
mC-G v. MDRD –
Evaluation of Carboplatin Dose Calculations
Mean Diff SD % CI P-value
C-G v. mC-G –
C-G v. MDRD –
mC-G v. MDRD –

11. Clinical Significance and Accuracy
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
Number % Achievement
C-G vs. mC-G
C-G vs. MDRD

12. Discussion/Conclusions
Differences exist between the C-G, mC-G, and 6-variable 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

13. Evaluation of the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (C-G) formulas in the Calvert equation for Carboplatin Dosing
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