MASSIVE CISPLATIN OVERDOSE BY ACCIDENTAL SUBSTITUTION FOR CARBOPLATIN- TOXICITY AND MANAGEMENT

Background. Unlike the related drug carboplatin, cisplatin is highly n ephrotoxic and must be given with vigorous intravenous hydration at a much lower dose. As the result of an accidental substitution of cispla tin for carboplatin, a 68-year-old woman received a massive overdose o f cisplatin without intravenous hydration. Methods. Laboratory documen tation included measurements of platinum concentrations by atomic abso rption spectroscopy and of xeroderma pigmentosum group E (XPE) binding factor, a protein that is involved in the recognition step of DNA rep air. Results. Toxicities included severe emesis, myelosuppression, ren al failure, and deafness, which are well known. Other toxicities were seizures, hallucinations, loss of vision, and hepatic toxicity, which were unusual and may have been caused by the magnitude of the overdose . As late as day 19, there was a continued cellular response from cisp latin, as evidenced by decreased levels of XPE binding factor in extra cts from the patient's peripheral blood lymphocytes. Plasmapheresis wa s effective in lowering the platinum concentration from greater than 2 900 ng/ml to 200 ng/ml and appeared to be of clinical benefit. Even af ter the onset of renal failure, hydration to increase urine volume res ulted in increased urinary excretion of platinum. Granulocyte-macropha ge colony-stimulating factor (GM-CSF) was used to ameliorate myelosupp ression. The patient received a transplanted kidney from her monozygot ic twin sister and survived with no clinically significant deficit exc ept for deafness. Conclusions. No previous reports exist of survival a fter such a high dose of cisplatin without intravenous hydration. In t he future, patients may benefit from similar management and heightened awareness of the possibility of accidental substitution.