Adverse Event Profiles of Platinum Agents: Data Mining of the Public Version of the FDA Adverse Event Reporting System, AERS, and Reproducibility of Clinical Observations

OBJECTIVE Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to confirm platinum agent-associated adverse events, and to clarify the rank-order of these drugs in terms of susceptibility. METHODS After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving cisplatin (CDDP), carboplatin (CBDCA), or oxaliplatin (L-OHP) were analyzed. Authorized pharmacovigilance tools were used for the quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. RESULTS Based on 1,644,220 AERs from 2004 to 2009, CDDP, CBDCA, and L-OHP all proved to cause nausea, vomiting, acute renal failure, neutropenia, thrombocytopenia, and peripheral sensory neuropathy. Higher susceptibility to nausea was found for CDDP than CBDCA and L-OHP. Acute renal failure was also more predominant for CDDP, and CBDCA did not increase the blood level of creatinine. A stronger association with thrombocytopenia was suggested for CBDCA. Susceptibility to peripheral sensory neuropathy was greatest for L-OHP, but less extensive for CDDP and CBDCA. CONCLUSION The results obtained herein were consistent with clinical observations, suggesting the usefulness of the FDA's adverse event reporting system, AERS, and the data mining method used herein.