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

1Calvert AH, et al. Clin Oncol 1989;7:1748-56. 2Duffull 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.

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;76:1067. 6Wright 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.

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, mC-G, 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)

Demographics n = 128Gender

Male 125Female 3Race

Non-African American 79African American 49

Characteristic Mean (+/-SD)Age, years 62.99 +/- 9.12TBW, kg 78.88 +/- 20.93BSA, m2 1.96 +/- 0.28SCr, mg/dL 1 +/- 0.30Albumin, g/dL 3.2 +/- 0.55

Table 1

Mean Diff SD 95% CI P-value C-G v. mC-G 5.83 12.58 3.63 – 8.03 <0.001C-G v. MDRD 4.73 24.13 0.511 – 8.95 0.028mC-G v. MDRD -1.09 25.91 -5.63 – 3.44 0.634

Evaluation of Carboplatin Clearance Calculations

Mean Diff. SD 95% CI P-valueC-G v. mC-G 6.05 109.6 -13.12 – 25.22 0.533C-G v. MDRD 7.64 183.46 -24.45 – 39.73 0.648mC-G v. MDRD 1.59 131.79 -21.47 – 24.64 0.892

Evaluation of Carboplatin Dose Calculations

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

Number % Achievement C-G vs. mC-G 3 3.13C-G vs. MDRD 32 25

Accuracy (30%) of Renal Estimations

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