Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease

Abstract

We have treated 38 transplant-eligible patients with relapsed/refractory non-Hodgkin's lymphoma and Hodgkin's disease using an outpatient-based regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and peripheral blood stem cell mobilisation. Patients included relapsed or refractory diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = 11), T-cell lymphoma (n = 2), mantle cell lymphoma (n = 2) and Hodgkin's disease (n = 6). Seven patients with diffuse large B-cell lymphoma and three patients with follicular lymphoma (26%) were considered chemorefractory. Cycles of ICE therapy were administered every 21 days as an outpatient and consisted of ifosfamide 5000 mg/m2 intravenously (i.v.) fractionated into three equally divided doses over 3 days, carboplatin [mg dose = 5 × area under the curve (AUC)] i.v. on day 1 and etoposide 100 mg/m2 i.v. daily for 3 days. Subsequently, granulocyte colony-stimulating factor (G-CSF) 5 μg/kg subcutaneously (s.c.) was administered daily from day +5. Of the 11 follicular lymphoma patients, 10 also received rituximab with ICE therapy. Median age of patients was 52 years (range 30-65). Patients received a mean of 2.6 cycles (range 1-4) of ICE. There were no toxic deaths and no significant non-haematological toxicities secondary to ICE therapy. Grade IV thrombocytopenia and grade IV neutropenia with at least one cycle of ICE were seen in 47% and 53% of patients, respectively. Median time to peripheral blood stem cell (PBSC) harvest was 14 days (range 10-20), while the median CD34+ cell yield was 5.2 × 106 cells/kg (range 2.3 × 106-27.2 × 106). Only one of the ICE-responders failed to mobilise PBSCs. The overall response rate to ICE was 87%, comprising 14 patients (37%) who achieved a complete response (CR) and 19 (50%) who achieved a partial response (PR). A total of 30 patients have undergone autologous stem cell transplantation (SCT) while two follicular lymphoma patients have received a non-myeloablative allogeneic SCT. Follow-up is short; however, the Kaplan-Meier estimate of the proportion of patients alive and event-free at a median follow-up of 11 months is 80% and 59%, respectively. Event-free survival for patients who achieved a CR after ICE and transplantation is 88% versus 45% for those who achieved a PR. These data confirm the efficacy and tolerability of fractionated ICE chemotherapy as both a salvage and mobilisation regimen that can be readily delivered in an outpatient setting.