Carboplatin Dosing: Area Under the Controversy. Kyle LaPorte, PharmD.

Transcription

1 Carboplatin Dosing: Area Under the Controversy Kyle LaPorte, PharmD.

2 Disclosure No relevant financial or non-financial conflicts of interest exist between the presenter and information discussed in this presentation

3 Objectives Pharmacy Technician Identify the medication carboplatin and describe its proper dosing regimen Name the two formulas utilized to calculate the creatinine clearance (CrCl) and carboplatin dose Pharmacist Calculate creatinine clearance (CrCl) and carboplatin dose using the Cockcroft-Gault equation and Calvert formula, respectively Compare and contrast issues with carboplatin dosing including what body weight and serum creatinine values used in estimation of renal function

4 Carboplatin Platinum analog Interferes with cellular replication through intercalation of DNA Indications FDA approved in 1989 for advanced ovarian cancer Multiple off-label indications (e.g. breast, lung, lymphoma, etc.) Kinetics Linear kinetics 65-70% renal clearance within 24 hours Toxicity Myleosuppression (neutropenia, thrombocytopenia) Nephrotoxicity

5 Carboplatin Dosing Dose is based on the desired area under the curve (AUC) Goal AUC range from 2-8 The Calvert Formula Carboplatin Dose = Target AUC x (GFR + 25) GFR originally estimated using 51 Cr-EDTA GFR now capped at 125 ml/min/1.73m 2 25 denotes non-renal clearance (e.g. irreversible tissue binding) Calvert AH, et al. J Clin Oncol 1989;7:

6 Calvert AH, et al. J Clin Oncol 1989;7: The Calvert Formula

7 GFR vs. CrCl for Carboplatin Isotope GFR determination will always be preferred over estimation Expensive Requires blood sampling Not readily available Cockcroft-Gault Found to be ideal method to estimate carboplatin clearance Inexpensive Readily available Craig AL, et al. Br J Cancer 2012;107;1310-6

8 Cockcroft-Gault Equation

9 What values to use in Cockcroft-Gault What body weight should be used for calculating CrCl? In what population is it appropriate to use an adjusted body weight? Is it appropriate to round SCr to pre-specified values in elderly or cachexic patients?

10 Weight Input for Cockcroft-Gault Actual Body Weight Designed and validated using Actual body weight Should be used for most patients Adjusted Body Weight Appropriate for patients with a BMI>30 kg/m 2 IBW x (Actual BW IBW) Ideal Body Weight Underestimates CrCl in most patients Exception, if underweight may overestimate

11 Weight Input for Cockcroft-Gault Age: 47 SCr: 1.0 mg/dl Height: 70 in Weight: 80 kg CrCl: 103 ml/min Age: 47 SCr: 1.0 mg/dl Height: 70 in Weight: 110 kg CrCl: 142 ml/min

12 Serum Creatinine (SCr) Surrogate marker for renal clearance, which is subject to much variability outside of renal function By-product of muscle metabolism SCr levels are low in patients with low muscle mass (e.g. elderly) Poor accuracy in patients with low SCr Often recommended to round-up to standard SCr values Use of reported SCr overestimates CrCl 0.7 vs. 0.8 vs. 1.0 mg/dl Should round-up to the lower limit of the laboratory assay

13 Serum Creatinine (SCr) Age: 47 SCr: 0.6 mg/dl Height: 70 in Weight: 80 kg CrCl: 172 ml/min AUC: 6 Carboplatin: 900 mg Age: 47 SCr: 1.0 mg/dl Height: 70 in Weight: 80 kg CrCl: 103 ml/min AUC: 6 Carboplatin: 770 mg

14 Conclusions Calvert formula is the preferred method of calculating carboplatin dose Cockcroft-Gault is the preferred equation calculate CrCl Actual body weight should be utilized in most patients Use adjusted body weight in obese patients (BMI >30 kg/m 2 ) Round-up low creatinine values to your institutional lower limit of normal Capping CrCl at 125 ml/min is recommended for majority of patients

15 Learning Assessment Pharmacy Technician How is the dose of carboplatin represented? a) mg/kg (based on actual body weight) b) mg/m 2 c) AUC d) mg/kg (based on ideal body weight) What is the preferred formula for calculating carboplatin dose? a) Egorin formula b) Calvert formula c) Newell formula d) Chatelut equation Pharmacist Which of the following is the preferred method GFR estimation for the Calvert formula? a) Cockcroft-Gault equation b) MDRD equation c) CKD-EPI equation d) 51 Cr-EDTA What variables are important to critically assess when calculating estimated GFR? a) Serum creatinine and body weight b) Patient height and BSA c) Cancer diagnosis and desired AUC d) Patients co-morbidities and concurrent medications