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: M J Rummel, K U Chow, T Karakas, E Jäger, J Mezger, U von Grünhagen, K P Schalk, O Burkhard, M L Hansmann, H Ritzel, L Bergmann, D Hoelzer, P S Mitrou
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 38 Issue 13 Pg. 1739-46 (Sep 2002) ISSN: 0959-8049 [Print] England
• PMID: 12175690 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Cladribine
• Mitoxantrone

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cladribine (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Humans
• Infusions, Intravenous
• Lymphoma, Mantle-Cell (drug therapy)
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage, adverse effects)
• Prospective Studies
• Treatment Outcome