Phase 2 study of mitozantrone in combination with chlorambucil and prednisolone for relapsed and refractory non‐Hodgkins lymphoma

Abstract

Thirty-six patients with non-Hodgkin's lymphoma (NHL) (comprising patients with refractory or relapsed disease and eight elderly, unfit patients with de novo disease) were treated with mitozantrone, chlorambucil and prednisolone on an out-patient basis. Fifteen patients had low grade (LG) disease, five patients intermediate grade (IG) disease and 16 patients high grade (HG) disease and 31/36 had stage IV disease. All elderly patients had IG or HG disease. The regimen was well-tolerated. After six courses of chemotherapy, there was a 69 per cent response rate with 33 per cent in complete remission. The median duration of remission was 15 months. The overall 3-year projected survival was 38 per cent; 27 per cent for LG disease and 47 per cent for HG and IG disease. Responses did not appear durable for either HG or LG disease unless CR was achieved early on. Three of the eight patients treated de novo (mean age 71 years) have survived disease-free, between 28 and 38 months from entry. This study indicates that mitozantrone-based regimens have promising activity in NHL and require further evaluation. The low toxicity combined with worthwhile remissions make this an attractive first-line option for elderly patients.

The addition of oral idarubicin to a chlorambucil/dexamethasone combination has a significant impact on time to treatment failure but none on overall survival in patients with low grade non-Hodgkin's lymphoma: Results of the Scotland and Newcastle Lymphoma Group randomized NHL VIII trial

“…This confirms the findings of previous studies [4,20] which suggested a role for anthracyclines in the treatment of LGNHL. The triple combination was well tolerated and, whilst the addition of the anthracycline added to overall toxicity, Grade IV toxicity was rare and there were no treatment related deaths.…”

“…The addition of vincristine and prednisolone resulted in a higher remission rate [3] but results for overall survival were disappointing. In 1990 preliminary results from a pilot study suggested some benefit from the addition of the anthracenedione, mitozantrone, to the combination of chlorambucil and prednisolone [4] and led to our phase II study of the efficacy of the addition of an oral anthracycline (idarubicin) to the combination of chlorambucil and dexamethasone (CID) [5]. Results from that study showed that the treatment was well tolerated and effective with a 5 year event free survival (EFS) of 22% and overall survival (OS) of 65%.…”