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.

Author(s): Kalinka-Warzocha E, Wajs J, Lech-Maranda E, Ceglarek B, Holowiecki J, Federowicz I, Walewski J, Czyz J, Robak T, Warzocha K, the Polish Lymphoma Research Group The following members of the Polish Lymphoma Research Group contributed to this article, Piotr Centkowski, MD, PhD (Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland), Kazimierz Sulek, MD, PhD (Department of Internal Medicine and Hematology, Military Institute of Medicine, Warsaw, Poland), Maria Blasinska-Morawiec, MD, PhD (Department of Proliferative Diseases, Regional Oncology Center, Lodz, Poland), Beata Stella-Holowiecka, MD, PhD (Department of Hematology, Silesian University of Medicine, Poland), Grzegorz Mazur, MD, PhD (Department of Hematology, Medical University of Wroclaw, Poland), Wieslaw W. Jedrzejczak, MD, PhD (Department of Internal Medicine, Hematology and Oncology, Medical University of Warsaw, Poland), Marzena Watek, MD (Department of Hemato-Oncology, Regional Oncology Center, Kielce, Poland), Przemyslaw Bilinski, MD, PhD (Institute of Hematology and Transfusion Medicine, Warsaw, Poland), Elzbieta Kisiel, MD (Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland).

Affiliation(s): Department of Proliferative Diseases, Regional Oncology Center, Lodz, Poland.

Publication date & source: 2008-05-09, Cancer., [Epub ahead of print]

Publication type:

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. Cancer 2008. (c) 2008 American Cancer Society.