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Keywords:

  • peripheral T-cell lymphoma;
  • not otherwise specified;
  • anaplastic lymphoma kinase-negative anaplastic large cell lymphoma;
  • angioimmunoblastic T-cell lymphoma;
  • chemotherapy;
  • multidrug resistant proteins

Abstract

BACKGROUND:

Patients with peripheral T-cell lymphomas (PTCLs) have inferior progression-free survival (PFS) and overall survival (OS) compared with patients who have aggressive B-cell non-Hodgkin lymphoma. Because PTCLs over express multidrug resistance gene 1/P-glycoprotein (MDR-1/P-gp), we devised platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) with agents that are not substrates of the efflux pump. Gemcitabine was included because of its excellent single-agent activity in PTCL.

METHODS:

Patients who had PTCL with stage II bulky disease, stage III or IV disease with extra-nodal, nodal, and transformed cutaneous presentations were eligible. Patients received intravenous cisplatin 25 mg/m2 on days 1 through 4, etoposide 40 mg/m2 on days 1 through 4, gemcitabine 1000 mg/m2 on day 1, and methylprednisolone 250 mg on days 1 through 4 of a 21-day cycle for 6 cycles.

RESULTS:

In total, 34 patients were enrolled, 33 were eligible, and 79% were newly diagnosed. Histologic types were PTCL not otherwise specified (n = 15), anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (n = 4), angioimmunoblastic T-cell lymphoma (n = 6), or other T-cell non-Hodgkin lymphomas (n = 8). Adverse events included 1 grade 5 infection with grade 3 or 4 neutropenia and 9 grade 4 hematologic toxicities. The overall response rate was 39% (47% in PTCL not otherwise specified, 33% in angioimmunoblastic T-cell lymphoma, 25% in ALK-negative and 38% in other T-cell non-Hodgkin lymphomas). The PFS rate at 2 years was 12% (95% confidence interval, 0.1%-31%), and the median PFS was 7 months. The OS rate at 2 years was 30% (95% confidence interval, 8%-54%), and the median OS was 17 months. Immunohistochemical analysis of P-gp expression revealed strong positivity in a subset of lymphoma cells (n = 6) and tumor endothelium (n = 25).

CONCLUSIONS:

Overall, PEGS was well tolerated, but OS was not considered promising given the design-specified targets. These results may serve as a benchmark for future comparisons for non-CHOP regimens. Cancer 2013. © 2012 American Cancer Society.