Long-term outcome of mesna, ifosfamide, mitoxantrone, etoposide (MINE) regimen as a consolidation in patients with aggressive non-Hodgkin lymphoma responding to CHOP

In aggressive non-Hodgkin lymphoma (NHL), CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) regimen has been standard for decades, and rituximab has increased response rates and survival in CD20 positive patients, recently. The aim of this prospective trial was to evaluate the long-term efficacy and toxicity of MINE as a consolidation treatment in aggressive NHL patients who had achieved CR or unproven CR after six cycles of CHOP in the first line setting. The primary end-point was disease-free-survival (DFS). Thirty-eight patients were enrolled between February 1992 and May 2000. All of the patients received two cycles of MINE (mesna 1.3 g/m2, ifosfamide 1.3 g/m2, etoposide 65 mg/m2 on days 1–3, and mitoxantrone 12 mg/m2 on day 1, every 3 weeks) following response to CHOP. Initial bulky disease sites were also applied radiotherapy. Male/female ratio was 1.53(23/15). Median age was 49(30–73). Most of the patients had advanced stage (84.2% for stage >3) and high IPI score (79% for IPI score >2). Sixty percent had diffuse large cell histology. Median follow-up time was 118 months (9–195). Actual mean dose intensity was 88%. There were seven febrile neutropenia episodes. Two patients had grade two neuropathy, one had grade three mucositis and another one had non-neutropenic pneumonia. There was no early toxic death. No serious late toxicity was observed during long-term follow-up. Five- and 10-year DFS rates were both 65.3%. DFS rate in the patients with more than two poor prognostic factors according to IPI score is remarkably high (88%). Five- and 10-year OS was 62.5 and 59%, respectively. MINE regimen seems to be effective as a consolidation regimen, especially, in intermediate/high risk patients and has low early and late toxicities, and it warrants to be evaluated in phase III randomised trials with rituximab in CD20 positive aggressive NHL patients.