Outpatient regimen rituximab plus ifosfamide, carboplatin and etoposide (R-ICE) for relapsed non-Hodgkin's lymphoma.

Approximately 1.5 million people worldwide are living with various forms of lymphoma, and it is estimated that 300 000 people will die each year. In terms of incidence and mortality, non-Hodgkin’s lymphoma (NHL) is the second fastest growing cancer in the USA and the third fastest growing in the rest of the world. Each year ∼60 000 people in the USA will be diagnosed with NHL. More than half of the patients with aggressive lymphoma are either primary refractory or, more often, relapse after their initial treatment. It has been shown that high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) does improve survival in patients treated in the first relapse [1]. Second-line chemotherapy regimens for relapsing patients with lymphoma generally include drugs not used during first-line therapy in order to avoid cross-resistant associations and cumulative toxicity. At the University of Nebraska Medical Center (UNMC), the ifosfamide, carboplatin and etoposide (ICE) regimen has been used for patients with relapsed aggressive NHL who are candidates for transplantation. As previously reported by Moskowitz et al. [2], this regimen has advantages of being effective for cytoreduction, results in minimal non-hematological toxicity, is not stem cell toxic and effectively mobilizes stem cells into peripheral blood. Hamlin et al. [3] showed that relapsed patients with diffuse large B cell lymphoma (DLBCL) and good risk disease [second-line age-adjusted international prognostic index (sAAIPI) I/II] are highly curable with ICE-based chemotherapy followed by high-dose chemotherapy and stem cell transplantation. Those patients may have a favorable long-term outcome and therefore need not be exposed to the risk of excessive toxicity of more intensive therapy. On the other hand, poor prognosis patients are candidates for more intensive therapies. Pilot trials using rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) have suggested an efficacy advantage in both indolent and aggressive B cell NHL, with no significant impact on toxicity. A more recently published randomized trial performed by the Groupe d’Étude des Lymphomes de l’Adulte (GELA) has shown that the addition of rituximab to the CHOP regimen increases the complete response (CR) rate and prolongs event-free survival (EFS) and overall survival (OS) in untreated elderly patients with diffuse large B cell lymphoma when compared with CHOP alone [4]. Preliminary results from Memorial Sloan–Kettering Cancer Center with rituximab plus ifosfamide, carboplatin and etoposide (R-ICE) in relapsed patients are promising, but the regimen requires inpatient treatment [5]. In some centers in the USA, there is a great need for the development of an outpatient regimen that is effective, tolerable and easy to deliver. With the aim of further improving the clinical response and prolonging EFS and OS of patients with relapsed and refractory aggressive NHL, R-ICE was investigated at the UNMC as an outpatient protocol. The objectives of the study were to determine the chemosensitivity rate in patients with recurrent or refractory NHL treated with ICE in combination with rituximab (R-ICE) and to determine whether rituximab changes the toxicity profile of ICE chemotherapy regimen in these patients.