Mitoxantrone and Fludarabine in the Treatment of Patients with Non-Hodgkin's Lymphoma Failing Primary Therapy with a Doxorubicin-or Mitoxantrone-Containing Regimen

Abstract

Patients with recurrent lymphoma of any grade were treated with mitoxantrone (12 mg/m² given intravenously (IV) over 15–30 minutes on day 1) followed by fludarabine at a dose of (25 mg/m 2 given IV over 30 minutes on days 1–3) every 28 days fludarabine at a dose of(25 mg/m² given IV over 30 minutes on days 1–3) every 28 days. All patients had failed one prior chemotherapy regimen that contained either doxorubicin or mitoxantrone, total dose not exceeding 350 mg/m² doxorubicin or 80 mg/m² mitoxantrone. mitoxantrone. Thirty one patients (22 with intermediate-or high-grade and 9 with low-grade NHL) were enrolled. Median age was 63 years (range: 21 to 87). The objective response rate for patients with intermediate/high-grade NHL was 55% (27% with CR) and 89% (56% with CR) for patients with low-grade NHL. Median time to disease progression was 5.1 months for patients with intermediate/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 months. Median time to death for patients with low-grade NHL was not calculable 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 neutropenia was reported in 80% (24 of 30) of patients and Grade 3/4 thrombocytopenia in 19% (6 of 31) of patients. Nine hospitalizations for adverse events (primarily fever and neutropenia) occurred among eight patients, all with intermediate/high-grade NHL, during a total of 118 cycles of therapy. Further studies of this combination regimen in patients with intermediate/high-grade NHL and studies combined with monoclonal antibodies in low-grade NHL are warranted.

Key Words:

• non-Hodgkin's lymphoma
• mitoxantrone
• fludarabine
• salvage therapy
• GM-CSF