Oral fludarabine in combination with doxorubicin and dexamethasone as first-line therapy for nodal peripheral T-cell lymphomas: early results of a prospective multicenter study

Cancer Chemother Pharmacol. 2012 Feb;69(2):387-95. doi: 10.1007/s00280-011-1711-z. Epub 2011 Jul 26.

Abstract

Purpose: Nodal peripheral T-cell lymphomas (PTCLs) have particularly poor prognoses. Few data enabling establishment of an accepted standard treatment modality for PTCLs are available. We hypothesized that fludarabine-based regimens are tolerable and effective in treatment for nodal PTCLs. Therefore, this study was to analyze the toxicity of, response rate for, and outcome of treatment for nodal PTCLs with oral fludarabine, doxorubicin, and dexamethasone (FAD).

Methods: Patients with PTCLs received FAD every 28 days, consisting of oral fludarabine at 40 mg/m(2) on days 1-3, doxorubicin at 50 mg/m(2) on day 1, and oral dexamethasone at 20 mg/day on days 1-5. Patients who did not exhibit disease progression received at least four courses of treatment.

Results: Thirty-one of 35 patients with previously untreated nodal PTCLs enrolled in the study from 2007 to 2008 were evaluable. The incidence of grade 3-4 neutropenia was 55%. Nine patients had to have dose reductions of fludarabine and doxorubicin, none of whom had grade 3 or 4 toxic effects at the lower dose. Five of 31 patients had pneumonitis. No treatment-related mortality occurred. The response rate for the entire patient population was 71%, and the complete remission rate was 48%. The PFS and OS rates at 2 years were 54.2 and 77.1%, respectively. Four patients had died of cancer progression at the time of this analysis. The serum lactate dehydrogenase level had a significant effect on PFS and OS.

Conclusion: The FAD regimen had encouraging efficacy with an acceptable toxicity profile in patients with nodal PTCLs.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Alopecia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Administration Schedule
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / mortality
  • Lymphoma, T-Cell, Peripheral / pathology
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neutropenia / chemically induced
  • Prospective Studies
  • Survival Rate
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives
  • Vomiting / chemically induced

Substances

  • Dexamethasone
  • Doxorubicin
  • Vidarabine
  • fludarabine