Fludarabine, mitoxantrone and dexamethasone as first line treatment of patients with indolent Non-Hodgkin's lymphoma (NHL): GATLA first interim report
Advanced stage (Stage III/IV) indolent NHL is generally thought to be incurable, but can be treated successfully with chemotherapy as well as immunotherapy with or without linked radionuclides. Fludarabine (F) chemotherapy is at least as effective, as conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL . Better response rates can be achieved by combining F with Mitoxantrone (N) and Dexamethasone (D) in indolent NHL patients.
The GATLA (Grupo Argentino de Tratamiento de la Leucemia Aguda) performed this phase II study to evaluate the use of FND as a first line treatment for low grade NHL . Sixty four patients were evaluated with disease stages: I: 5.8%, II: 14.5%, III: 24.6% and IV: 55%. They received 6 cycles of FND.
70% of patients (48 pts) achieved complete response (CR), 23% (16 pts) achieved partial response (PR) and progressive disease was seen in 7% (5 pts). Overall survival at 24 months was 90%.
This study was not randomized, so it is difficult to know the accuracy of the results. It seems likely that this regimen compares with other standard regimens, but there are other therapies which may be superior. About 20% of the patients had Stage I or II disease, which could potentially be curable with the addition of external beam radiation therapy, however it is unclear radiation was part of their treatment.
Bexxar radioimmunotherapy for first line treatment of follicular lymphoma (Kaminski et al) appears to be as good as, or better, than the results of this study using FND. Using Bexxar as initial treatment, the complete response rate was 75%, the progression free survival at 2 years was over 65%, and at 5 years, 59%. Longer follow-up from this study will be needed to determine how long the response lasts.
The optimal initial treatment for indolent lymphoma is an open question. For early stage disease, cure may be possible using external beam radiation. In advanced stage disease, the goal is obtain the most reliable and longest lasting responses with minimum toxicity.