Mitoxantrone and fludarabine in the treatment of patients with non-Hodgkin's lymphoma failing primary therapy with a doxorubicin- or mitoxantrone-containing regimen

Patients with recurrent lymphoma of ally grade were treated with mitoxantro ne (12 mg/m(2) given intravenously (IV) over 15-30 minutes on day 1) follow ed by fludarabine at a dose of (25 mg/m(2) given IV over 30 minutes on day s 1-3) every 28 days fludarabine at a dose of(25 mg/m(2) given IV over 30 m inutes on days 1-3) every 28 days. All patients had failed one prior chemot herapy regimen that contained either doxorubicin or mitoxantrone, total dos e not exceeding 350 mg/m(2) doxorubicin or 80 mg/m(2) mitoxantrone. mitoxan trone. Thirty one patients (22 with intermediate- or high-grade and 9 with low-grade NHL) were enrolled. Median ape was 63 years (range: 21 to 87). Th e objective response rats For patients with intermediate/high-grade NHL was 55% (27% with CR) and 89% (56% with CR) for patients with low-grade NHL. M edian time to disease progression was 5.1 months for patients with intermed iate/high-grade NHL and 10.8 months for patients with low-grade NHL. Median time to death for patients with intermediate/high-grade disease was 11.4 m onths. Median time to death for patients with low-grade NHL was not calcula ble as only one death (due to respiratory Failure) occurred in this group 6 .5 months after study start. The regimen was well tolerated. Grade 3/4 neut ropenia was reported in 80% (24 of 30) of patients and Grade 3/4 thrombocyt openia in 19% (6 of 31) of patients. Nine hospitalizations for adverse even ts (primarily fever and neutropenia) occurred among eight patients, all wit h intermediate/high-grade NHL. during a total of 118 cycles of therapy. Fur ther studies of this combination regimen in patients with intermediate/high -grade NHL and studies combined with monoclonal antibodies in low-grade NHL are warranted.