Report of a Phase II Study of Proteasome Inhibitor Bortezomib (Velcade) in Patients with Relapsed or Refractory T-Cell Lymphoma.

The 26S proteasome plays a vital role in degrading regulatory proteins such as p53, p21, p27, NF-kB, I-kB, and bcl-2, that govern cell cycle, transcription factors activation, apoptosis and cell trafficking. Thus, the mechanisms by which bortezomib elicits its antitumor activity may vary among tumor types, and the extent to which each affected pathway is critical to the inhibition of tumor growth could also differ. The aim of this study was to determine the efficacy and toxicity of bortezomib in previously pretreated patients with peripheral T-cell lymphoma unspecified (PTCLU) and cutaneous T-cell lymphomas (CTCL). Each patient had to meet the following inclusion criteria to be enrolled in the study: histologically confirmed PTCLU or CTCL (according to REAL/WHO classification); any stage, any IPI, any bone marrow status; second or more relapse or refractory disease; age ≥ 18; ECOG performance status ≤ 2; Hb ≥ 10 g/dL, ANC ≥ 1.5x10⁹/L and platelets ≥ 100 x 10⁹/L; normal hepatic, renal and cardiac functions; and voluntary written informed consent. Bortezomib was given at 1.3 mg/m² IV push on days 1, 4, 8 and 11 every 21 days. Restaging was done every 2 cycles. Patients were treated for up to a total of 6 cycles unless removed from study for failure to respond or toxicity. The response criteria were those recommended by NCI sponsored Working Group. A total of 30 patients will be enrolled; so far 10 patients entered and preliminary results of this trial will be presented.