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1/ Why is carboplatin the only chemotherapy we dose by AUC?
A short tweetorial brought to you from a question posed by @FreedoBaggins.
Bottom Line: Chemo is Cool!
#MedEd #HemeTwitter
A short tweetorial brought to you from a question posed by @FreedoBaggins.
Bottom Line: Chemo is Cool!
#MedEd #HemeTwitter
2/ What is AUC (Area under the curve)?
Mathematically it is the âintegral of a curve describing variation of drug concentration over timeâ
Perhaps more helpfully, it functionally describes total drug exposure over time
Mathematically it is the âintegral of a curve describing variation of drug concentration over timeâPerhaps more helpfully, it functionally describes total drug exposure over time
3/ For almost all chemotherapy agents, you would ideally want to dose by AUC if you could.
Most chemotherapy toxicities are proportional to (drug concentration
time), which makes sense: higher concentration -> longer itâs around -> more toxicities.
Most chemotherapy toxicities are proportional to (drug concentration
time), which makes sense: higher concentration -> longer itâs around -> more toxicities.
4/ But truly calculating AUC requires multiple data points of drug concentrations at various time points. How is it that we can estimate the AUC of a drug without checking drug concentrations? What is special about carboplatin that lets us do it literally every day?
5/ Carboplatin is the only chemotherapy that is cleared entirely by glomerular filtration.
liver metabolism
renal secretion
renal absorption
Therefore, you can reliably predict its AUC from a single bolus dose based on a patientâs GFR.
liver metabolism renal secretion renal absorptionTherefore, you can reliably predict its AUC from a single bolus dose based on a patientâs GFR.
6/ When all is said and done, if you want an AUC of 6 (a common target dose), you can use the empirically-derived Calvert formula:
Total carboplatin dose in mg = Target AUC (mg*min/ml) x (estimated creatinine clearance + 25) mg/min. The units work out. https://pubmed.ncbi.nlm.nih.gov/2681557/
Total carboplatin dose in mg = Target AUC (mg*min/ml) x (estimated creatinine clearance + 25) mg/min. The units work out. https://pubmed.ncbi.nlm.nih.gov/2681557/
7/ Interesting Historical Notes:
When carboplatin was first developed in 1981, it was dosed based upon BSA like most other chemo (400mg/m2). This resulted in the significant mis-dosing (both over- and under-) of many patients.
When carboplatin was first developed in 1981, it was dosed based upon BSA like most other chemo (400mg/m2). This resulted in the significant mis-dosing (both over- and under-) of many patients.
8/ Eight years later, Calvert did a study showing that they could avoid excess toxicity and get better effects by dosing based off AUC predictions from GFR.
It has been the standard of care ever since.
It has been the standard of care ever since.
