Pixantrone dimaleate in combination with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: phase 1 study with a dose-expansion cohort.
BACKGROUND
Pixantrone dimaleate (pixantrone) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models. FND-R, a combination regimen of fludarabine, mitoxantrone, dexamethasone, and rituximab, has been shown to be an effective regimen for low-grade lymphomas.


METHODS
This dose-escalation study, with an expansion cohort, was conducted to evaluate the safety and preliminary efficacy of FPD-R, in which pixantrone was substituted for mitoxantrone in the FND-R regimen, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (NHL). Escalated doses of pixantrone were administered to newly enrolled patients on day 2 of each 28-day cycle of FPD-R.


RESULTS
Twenty-eight of 29 enrolled patients received at least 1 cycle of FPD-R (median, 5 cycles). Pixantrone 120 mg/m(2) was identified as the recommended dose in this regimen. Grade 3-4 adverse events were primarily hematologic; grade 3-4 lymphopenia occurred in 89% of patients and leukopenia in 79%. No patients developed congestive heart failure or grade 3-4 cardiac adverse events. Left ventricular ejection fraction decreases occurred in 8 (29%) patients, and most were grade 1 or 2, transient, and asymptomatic. The overall response rate was 89%. Estimated survival was 96% after 1 year and 92% after 3 years.


CONCLUSIONS
The FPD-R regimen was well-tolerated and highly active in patients with relapsed or refractory indolent NHL.