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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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. Cancer

Original languageEnglish (US)
Pages (from-to)5067-5073
Number of pages7
Issue number22
StatePublished - Nov 15 2011
Externally publishedYes


  • antineoplastic combined chemotherapy
  • indolent non-Hodgkin lymphoma
  • non-Hodgkin lymphoma
  • phase 1 clinical trial
  • pixantrone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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