MINE (mesna, ifosfamide, mitoxantrone, etoposide) Chemotherapy as a Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Abstract

PURPOSE: The prognosis of non-Hodgkin's lymphoma (NHL) is disappointing for patients who experience primary treatment failure or relapse after an initial response. Patients in relapse may respond again to chemotherapy, however the time to disease progression becomes shorter and eventually the disease becomes resistant. The aim of this study was to evaluate the efficacy and safety of the MINE regimen in the treatment of patients with relapsed or refractory NHL. MATERIAL AND METHODS: Forty-three pretreated patients with a median age of 56 years were enrolled into the study between October 1995 and June 2000. Most patients (60.5%) had a performance status of 0 to 1, and a diffuse large cell subtype (55.8%). Seventy-four percent of patients had stage III or IV disease at the start of MINE treatment. Eighteen (41.9%) patients had complete response, 5 (11.6%) had partial response, and 20 (46.5%) had failed to respond to prior therapy. Ifosfamide 4 g/m2 was divided over 3 days and administered IV over a 1 hour period. Mitoxantrone 8 mg/m2 was administered as a short IV infusion on day 1. Etoposide (65 mg/m2/day) was infused over 1 hour on days 1 to 3. A total of 144 cycles was administered, with a mean of 3.34 cycles per patient (range, 1-8). The mean relative dose intensity was 87.4%. RESULTS: 1) Nine patients achieved a complete response and nine patients achieved a partial response, resulting in an overall response rate of 43.8% of the 41 assessable patients. 2) The median survival time was 6 months (95% CI, 4 to 8 months), and the median time to failure was 5 months (95% CI, 3 to 7 months). 3) A statistically significant association with complete response rates was found for complete response to prior therapy (p=0.049). The significant factors for overall survival were a complete response after MINE chemotherapy and serum 2-microglobulin (p=0.003, p=0.012, respectively). The significant factors for time to treatment failure were a complete response after MINE chemotherapy and serum 2-microglobulin (p=0.003, p=0.044, respectively). 4) The main result of toxicity of MINE was bone marrow suppression. CONCLUSION: The response to MINE chemotherapy and serum 2-microglobulin were both independent prognostic factors for overall survival and time to treatment failure. As the median time to treatment failure for complete responses was 14 months, the best use of this regimen could be in a strategy that includes prompt consolidation of a complete response with intense chemotherapy, with or without hematopoietic stem cell rescue.