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Impact of Isotope Dilution Mass Spectrometry (IDMS) Standardization on Carboplatin Dose and Adverse Events
Author(s) -
Lawson Justin,
Switchenko Jeffrey M.,
McKibbin Trevor,
Donald Harvey R.
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1759
Subject(s) - carboplatin , medicine , dosing , concomitant , renal function , creatinine , toxicity , therapeutic drug monitoring , urology , chemotherapy , pharmacokinetics , cisplatin
Background When using area under the concentration–time curve–based strategies for dosing carboplatin, accurate estimation of glomerular filtration rate is required for determining dose. Commonly, the Cockcroft–Gault equation is used, which is dependent on measurement of serum creatinine ( SC r). Because analysis of SC r changed to an isotope dilution mass spectrometry ( IDMS ) standard, we sought to determine the impact of this assay change on carboplatin dosing and related toxicity. Methods This was a single‐center, retrospective chart review of adults treated with carboplatin between April 2008 and April 2010 divided into cohorts that initiated carboplatin before or after IDMS standardization. End points included grade 3 thrombocytopenia, decrease in platelet count, and hospitalization and were evaluated in cohorts based on concomitant chemotherapy. Results The chart review identified 158 patients, with 63 patients in the pre‐ IDMS group and 95 patients in the post‐ IDMS group. Average SC r (pre 1.01 mg/dl vs post 0.86 mg/dl, p<0.001) and average carboplatin dose (pre 580 mg vs post 703 mg, p<0.001) were significantly different between the groups. The frequency of grade 3 thrombocytopenia was not statistically significant across three partner chemotherapy cohorts before and after IDMS implementation. Conclusion IDMS standardization led to an overall decrease in SC r with subsequent increase in carboplatin doses. However, no increase in recorded adverse events was observed, suggesting that the clinical relevance in toxicity from higher doses was minimal.