Incidence of ifosfamide-induced neurotoxicity in lymphoma patients receiving fractionated ICE-based chemotherapy

Abstract

6677 Background: Ifosfamide-induced neurotoxicity is a treatment-related complication that is increasingly being reported. Here, we describe the incidence and presentation of neurotoxicity in our patients. Methods: We reviewed all Hodgkin's and Non-Hodgkin's lymphoma patients who received fractionated ICE (D1–3: ifosfamide 2g/m2 over 2h with an equivalent dose of mesna over 12h, carboplatin [AUC=5 divided equally between 3 days; max=800mg] over 1h, etoposide 75mg/m2 over 2h; cycles were repeated q28 days) +/- rituximab. Patients who experienced any neurologic symptom prior to initiation of chemotherapy were excluded. Results: Between July 2001 and May 2003, 19 patients received a total of 56 cycles. All had relapsed or refractory disease. Six patients presented with neurologic symptoms all on cycle 1 including 3 in whom dosage reductions were made. Of the 3 who went on to subsequent cycles, all with dosage reductions, 1 had a recurrent episode. Symptoms included one or more of the following: confusion (n=7), mood alterations (n=3), hallucinations (n=2), and somnolence (n=4). Of these, grade 3 toxicities occurred in 3 cases: confusion (n=1), hallucinations (n=1), and somnolence (n=1). There were no episodes of seizures. Symptoms were noted within 48–72h after the first dose of ifosfamide and in 6 of 7 cases resolved within 1–7 days. Treatment of symptoms involved the use of methylene blue alone in 2 cases and thiamine combined with methylene blue in 1 case. Previously identified risk factors such as renal and hepatic impairment, prior cisplatin, prior cranial radiation, albumin < 30g/L, pelvic/intra-abdominal involvement, and stage and type of disease were analyzed. Multivariate analysis identified renal impairment and low albumin as independent risk factors in our cohort. Concomitant use of rituximab was not identified as a risk. Conclusions: Fractionated ICE-based chemotherapy is associated with a high incidence of ifosfamide-induced neurotoxicity in relapsed or refractory lymphoma patients. No significant financial relationships to disclose.