Advances in Pharmacoepidemiology and Drug Safety

Abstract

Ifosfamide Induced Neurotoxicity Secondary to Concomitant Aprepitant Use

Akshiv Malhotra, Bernard J. Poiesz, Andrew W. Burgdorf and Ajeet Gajra

Ifosfamide is an alkylating agent, a structural analogue of cyclophosphamide. In its initial days its use was limited secondary to dose limiting hemorrhagic cystitis which was counteracted by using mesna (2-mercaptoethane sulphonate) along with it [1]. Ifosfamide has found several uses since then. One of its most important uses is in advanced soft tissue sarcomas where it is used as adjuvant chemotherapy along with doxorubicin [2,3]. The Italian cooperative trial showed 5-year overall survival estimate to be 66.0% and 46.1% for the treatment and the control groups, respectively (p=0.04) [4]. Ifosfamide and doxorubicin are also used with good results in advanced rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Group trial showed a complete response rate of 52% in patients treated with these 2 drugs [5]. Also, ifosfamide along with etoposide was found to be superior to vincristine and melphalan in another study for advanced rhabdomyosarcoma with an overall survival rate going up to 55% at 3 years [6]. In a study for Ewing’s sarcoma, cyclophosphamide and ifosfamide were found to have similar efficacy but the former was associated with higher rate of toxicity [7]. In children with recurrent/ refractory sarcoma, treatment with ifosfamide, carboplatin and etoposide (ICE) as re-induction chemotherapy produced an overall response rate of 51% with a significant improvement in overall survival at 1 and 2 years [8]. Furthermore, in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) the overall response rate to ICE was found to be as high as 70%, with a complete response rate of 25% to 30% [9]. When this regimen was combined with rituximab (R), an even better response was seen [10].