title: Fewer infections, but maintained antitumor activity with lower-dose versus standard-dose cladribine in pretreated low-grade non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine [2-CDA]) administered at two different dosages.
  
  
  METHODS
  In this two-cohort study, patients with low-grade refractory/relapsing non-Hodgkin's lymphoma (NHL) received 2-CDA at a dose of 0.7 mg/kg per cycle as a continuous intravenous (i.v.) infusion (group 1, n = 44) or at a reduced dose of 0.5 mg/kg per cycle as a subcutaneous (s.c.) bolus injection (group 2, n = 60). Three 2-CDA cycles at > or = 4-week intervals were planned, then treatment could be pursued until six cycles.
  
  
  RESULTS
  A total of 300 cycles were administered (group 1, 114 cycles; group 2, 186). Patient characteristics in both groups were comparable. The median dose-intensities were 0.17 mg/kg/wk and 0.13 mg/kg/wk for groups 1 and 2, respectively (P < or = .0001). The overall response rate for all 104 patients was 54% (95% confidence interval [CI], 45% to 66%; 15% complete response [CR] and 39% partial response [PR]). Response was similar in both patient groups (57% in group 1 and 53% in group 2; P = .72), and no association between 2-CDA dose-intensity and response rate was found (P = .35). Median remission duration was 7 and 12 months in groups 1 and 2, respectively (P = .21). Toxicity, in particular opportunistic infections (> or = grade 2, 30% in group 1 v 7% in group 2; P = .003) and myelosuppression (> or = grade 3 neutropenia, 33% v 8% of 2-CDA cycles, P < .0001), were more frequent in group 1. Multiple logistic regression analysis showed that the infection risk (grade > or = 2) was decreased by 81% with 2-CDA dose reduction in group 2 after adjusting for number of pretreatment regimens and time since diagnosis (P = .01).
  
  
  CONCLUSIONS
  When administered as a s.c. bolus injection, 2-CDA at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.
authors.affiliation: Institute of Medical Oncology, University of Bern, Inselspital, Switzerland. daniel.betticher@insel.ch
authors.forename: D C
authors.initials: DC
authors.lastname: Betticher
authors.forename: A
authors.initials: A
authors.lastname: von Rohr
authors.forename: D
authors.initials: D
authors.lastname: Ratschiller
authors.forename: S F
authors.initials: SF
authors.lastname: Schmitz
authors.forename: T
authors.initials: T
authors.lastname: Egger
authors.forename: T
authors.initials: T
authors.lastname: Sonderegger
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
authors.forename: T
authors.initials: T
authors.lastname: Kroner
authors.forename: G B
authors.initials: GB
authors.lastname: Zulian
authors.forename: F
authors.initials: F
authors.lastname: Cavalli
authors.forename: M F
authors.initials: MF
authors.lastname: Fey
authors.forename: T
authors.initials: T
authors.lastname: Cerny
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D017338:Cladribine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D016015:Logistic Models; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000453:epidemiology*; D011446:Prospective Studies; D012074:Remission Induction; D012306:Risk; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine