title: Phase 2 trial of combined cisplatin, etoposide, gemcitabine, and methylprednisolone (PEGS) in peripheral T-cell non-Hodgkin lymphoma: Southwest Oncology Group Study S0350.
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/m(2) on days 1 through 4, etoposide 40 mg/m(2) on days 1 through 4, gemcitabine 1000 mg/m(2) 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.
authors: Section of Hematology, University of Arizona/Arizona Cancer Center, Tucson, Arizona 85724, USA. dmahadevan@azcc.arizona.edu
authors: Daruka
authors: D
authors: Mahadevan
authors: Joseph M
authors: JM
authors: Unger
authors: Catherine M
authors: CM
authors: Spier
authors: Daniel O
authors: DO
authors: Persky
authors: Fay
authors: F
authors: Young
authors: Michael
authors: M
authors: LeBlanc
authors: Richard I
authors: RI
authors: Fisher
authors: Thomas P
authors: TP
authors: Miller
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003841:Deoxycytidine; D005047:Etoposide; D002945:Cisplatin; D008775:Methylprednisolone; D000093542:Gemcitabine