Survey of Carboplatin Dosing Strategies
Survey of Carboplatin Dosing Strategies
In October 2010, the Food and Drug Administration (FDA) issued a communication to the oncology community regarding measurement of SCr for use in MCFs. FDA stated that the isotope dilution mass spectrometry method used to measure SCr renders values that cause overestimation of GFR determined by formulae when SCr values are less than 0.8 mg/dL. Therefore, FDA directed that the carboplatin label state that GFR should not exceed 125 mL/min in patients with normal renal function. Although this is a step toward resolving the issues illustrated by the current study, it does not address the variations of formulae used and the different assumptions used to calculate carboplatin doses with those formulae. The abstract of our study was presented before the FDA letter was released; therefore, the option for capping the CrCl was not included in our survey.
Although the use of the actual SCr, actual body weight, and Cockcroft-Gault in MCFs was most common, no consistency was observed in responses for dosing carboplatin. We can only speculate what actually is occurring in practice. In the case example, 27 (57.5%) participants indicated overdosing, 9 (19%) indicated underdosing, and 11 (23.5%) were within 100 mg of our dose (n = 47). The average dose of 978 mg was 257 mg higher than our calculated dose.
We have searched the literature and standardized our carboplatin AUC dose calculation methods. We use the MCF with CG. We use actual body weight unless the patient's body mass index (BMI) is greater than 30 kg/m. If BMI is greater than 30 kg/m, we use adjusted body weight. For SCr values less than 0.8 mg/dL, we round up SCr to 0.8 mg/dL. Only a large prospective trial can determine if our methods produce carboplatin doses that are sufficiently accurate to compare with the original CF, but at least we are confident that we are using methods that are derived from published peerreviewed research and that all our patients of the same weight, age, SCr, and sex will receive the same dose of carboplatin for a prescribed AUC.
Discussion
Carboplatin Dosing: Updates and Existing Issues
In October 2010, the Food and Drug Administration (FDA) issued a communication to the oncology community regarding measurement of SCr for use in MCFs. FDA stated that the isotope dilution mass spectrometry method used to measure SCr renders values that cause overestimation of GFR determined by formulae when SCr values are less than 0.8 mg/dL. Therefore, FDA directed that the carboplatin label state that GFR should not exceed 125 mL/min in patients with normal renal function. Although this is a step toward resolving the issues illustrated by the current study, it does not address the variations of formulae used and the different assumptions used to calculate carboplatin doses with those formulae. The abstract of our study was presented before the FDA letter was released; therefore, the option for capping the CrCl was not included in our survey.
Evaluation of Survey Findings
Although the use of the actual SCr, actual body weight, and Cockcroft-Gault in MCFs was most common, no consistency was observed in responses for dosing carboplatin. We can only speculate what actually is occurring in practice. In the case example, 27 (57.5%) participants indicated overdosing, 9 (19%) indicated underdosing, and 11 (23.5%) were within 100 mg of our dose (n = 47). The average dose of 978 mg was 257 mg higher than our calculated dose.
Authors' Observations
We have searched the literature and standardized our carboplatin AUC dose calculation methods. We use the MCF with CG. We use actual body weight unless the patient's body mass index (BMI) is greater than 30 kg/m. If BMI is greater than 30 kg/m, we use adjusted body weight. For SCr values less than 0.8 mg/dL, we round up SCr to 0.8 mg/dL. Only a large prospective trial can determine if our methods produce carboplatin doses that are sufficiently accurate to compare with the original CF, but at least we are confident that we are using methods that are derived from published peerreviewed research and that all our patients of the same weight, age, SCr, and sex will receive the same dose of carboplatin for a prescribed AUC.
