Acute encephalopathy: A new toxicity associated with high-dose paclitaxel

The purpose of this study was to describe acute encephalopathy as a new tox icity associated with paclitaxel, when it is delivered at high doses (great er than or equal to 600 mg/m(2)) with stem cell support. A total of 129 pat ients, included in clinical trials of paclitaxel-containing high-dose chemo therapy, were analyzed. A total of 114 patients received paclitaxel at a do se of greater than or equal to 600 mg/m(2). Six patients presented acute en cephalopathy starting between 7 and 23 days after paclitaxel treatment; two of them had received prior whole-brain irradiation. Paclitaxel was given a lone (one patient), with cyclophosphamide and cisplatin (two patients), and with cyclophosphamide a nd cisplatin plus 1,3-bis(2-chloroethyl)-1-nitroso urea (three patients). Central nervous system toxicity consisted of rapid o btundation and coma (five patients) and severe confusional picture with par anoid ideations (one patient). Brain magnetic resonance imaging showed diff use white matter atrophy (one patient) or multiple small infarcts (one pati ent), or it was normal (four patients), Other complementary tests, includin g cerebrospinal fluid analysis and electroencephalography, were nondiagnost ic, An effect from concomitant psychotropic medications or from other organ toxicities was excluded in all patients. Three patients recovered after 8- 15 days, either spontaneously (two patients) or after high-dose steroids (o ne patient). Three patients died of irreversible coma. Necropsy, performed in two patients, showed generalized white matter atrophy and multiple brain parenchymal infarcts, respectively, No pharmacodynamic correlation between the occurrence of encephalopathy and a pharmacokinetic parameter of paclit axel could be identified. Paclitaxel-containing high-dose chemotherapy can cause severe acute encephalopathy, An aggravating effect from prior brain i rradiation or concurrent 1,3-bis(2-chloroethyl)-1-nitrosourea seems possibl e.