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.

Abstract

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.

• Authors: Tomasz P Srokowski, James E Liebmann, Manuel R Modiano, Gary I Cohen, Barbara Pro, Jorge E Romaguera, Christine Kuepfer, Jack W Singer, Luis E Fayad
• Journal: Cancer (Cancer) Vol. 117 Issue 22 Pg. 5067-73 (Nov 15 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21681734 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Isoquinolines
• Rituximab
• Dexamethasone
• pixantrone
• Vidarabine
• fludarabine

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Dexamethasone (administration & dosage)
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Humans
• Isoquinolines (administration & dosage)
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Recurrence
• Retreatment
• Rituximab
• Vidarabine (administration & dosage, analogs & derivatives)