title: Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low-grade B-cell non-Hodgkin lymphoma patients: final report of the Polish Lymphoma Research Group.
abstract: BACKGROUND
  The objective of this study was to compare the efficacy of 3 regimens, cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination in previously untreated patients with low-grade B-cell non-Hodgkin lymphoma (LGNHL).
  
  
  METHODS
  For this 3-arm, phase 3 study, 197 patients were randomly allocated to receive 6 monthly courses of cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination. Patients for whom all clinical data were available and 162 patients who completed scheduled chemotherapy were analyzed for the endpoints of this study.
  
  
  RESULTS
  Compared with cyclophosphamide, vincristine, and prednisone combination regimen, cladribine alone or cladribine and cyclophosphamide combination induced higher probability of overall response (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7-9,3; P = .002, and OR = 8.5; 95% CI, 3.2-22.7; P < .0001, respectively), complete remission (OR = 5.8; 95% CI, 1.8-18.5; P = .003; and OR = 14; 95% CI, 4.4-44; P < .0001, respectively), progression-free survival (log-rank test P < .0001), but not overall survival. After incorporating the International Prognostic Index in multivariate analysis, treatment with cladribine-containing regimens remained an independent prognostic factor for progression-free survival (chi(2) = 35.94; hazard ratio = 2.38; P < .0002). Incidences of infections were similar in the randomized groups, whereas cladribine and cyclophosphamide combination, but not cladribine alone, induced more frequent neutropenia, anemia, and thrombocytopenia compared with cyclophosphamide, vincristine, and prednisone combination (P < .05 for each). This resulted in a higher frequency of prolongation of intervals between cladribine and cyclophosphamide combination and cyclophosphamide, vincristine, and prednisone combination cycles (P < .05), but dose reductions due to hematological or other toxicity did not differ significantly in cladribine alone, cladribine and cyclophosphamide combination, and cyclophosphamide, vincristine, and prednisone combination groups.
  
  
  CONCLUSIONS
  For patients with LGNHL, first-line cladribine alone or cladribine and cyclophosphamide combination regimens both provided similar treatment responses, acceptable toxicity, and better response rates than cyclophosphamide, vincristine, and prednisone combination.
authors.affiliation: Department of Proliferative Diseases, Regional Oncology Center, Lodz, Poland. warzocha@ihit.waw.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Kalinka-Warzocha
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Wajs
authors.forename: Ewa
authors.initials: E
authors.lastname: Lech-Maranda
authors.forename: Bernadetta
authors.initials: B
authors.lastname: Ceglarek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Irena
authors.initials: I
authors.lastname: Federowicz
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Czyz
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011044:Poland; D011241:Prednisone / Q000627:therapeutic use*; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D017338:Cladribine; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone