title: Reduced-dose cladribine (2-CdA) plus mitoxantrone is effective in the treatment of mantle-cell and low-grade non-Hodgkin's lymphoma.
abstract: Cladribine (2-chlorodeoxyadenosine) (2-CdA) has been shown to be effective in mantle-cell (MCL) and low-grade lymphomas (lgNHL). The aim of this multicentre study was to evaluate the rate and duration of remissions and to examine the toxicity of the combination of reduced-dose 2-CdA and mitoxantrone (CdM) in MCL and lgNHL as first-line therapy or for patients in their relapse. A total of 285 courses, median of five courses per patient, were administered to 62 evaluable patients (42 previously untreated, 20 relapsed) with 5 mg/m(2) 2-CdA per day given as an intermittent 2-h infusion over 3 consecutive days combined with 8 mg/m(2) mitoxantrone on days 1 and 2 for the untreated patients or 12 mg/m(2) mitoxantrone on day 1 for patients in their first relapse for a maximum of six cycles every four weeks. 32 follicular, 18 MCL, 9 lymphoplasmacytoid, 2 marginal zone and 1 unclassified low-grade B-cell lymphoma were involved in the study. 56 of the 62 patients responded to CdM resulting in an overall response rate of 90% (95% confidence interval (CI), 80-96%) with a complete remission (CR) rate of 44% (95% CI, 31-57%) and a median duration of remission of 25 months (range 6-42+). The overall survival rate at 48 months was 80%. For 42 previously untreated patients, the overall response rate was 88% (95% CI, 74-96%) with a CR rate of 38% (95% CI, 24-54%), whereas the response rate for the group of 20 previously treated patients was similar with a 95% overall response (95% CI, 75-100%) and a CR rate of 55% (95% CI, 32-77%). In MCL, CdM showed a high activity, achieving a response rate of 100% (95% CI, 81-100%) with a CR rate of 44% and a median duration of remission of 24 months (range 6-35+). Myelosuppression was the major toxicity with 23% grade 3 granulocytopenia and 50% grade 4. Thrombocytopenia was less commonly observed, with only 8% grades 3 and 4. These results demonstrate that the combination of reduced-dose 2-CdA and mitoxantrone is a highly active regimen in the treatment of low-grade lymphomas, and in particular of MCL.
authors.affiliation: Department of Internal Medicine, Hematology/Oncology, University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany
authors.forename: M J
authors.initials: MJ
authors.lastname: Rummel
authors.forename: K U
authors.initials: KU
authors.lastname: Chow
authors.forename: T
authors.initials: T
authors.lastname: Karakas
authors.forename: E
authors.initials: E
authors.lastname: Jäger
authors.forename: J
authors.initials: J
authors.lastname: Mezger
authors.forename: U
authors.initials: U
authors.lastname: von Grünhagen
authors.forename: K P
authors.initials: KP
authors.lastname: Schalk
authors.forename: O
authors.initials: O
authors.lastname: Burkhard
authors.forename: M L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: H
authors.initials: H
authors.lastname: Ritzel
authors.forename: L
authors.initials: L
authors.lastname: Bergmann
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: P S
authors.initials: PS
authors.lastname: Mitrou
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D017338:Cladribine; D008942:Mitoxantrone