Beneficial effect of chlorambucil in steroid-dependent and cyclophosphamide-resistant minimal change nephrotic syndrome.
BACKGROUND
Little information is available on the effect of second cytotoxic therapy in steroid-dependent children with minimal change nephrotic syndrome (MCNS).


METHODS
Response to second cytotoxic therapy and side effects were reviewed in 33 steroid-dependent and cyclophosphamide-resistant children with MCNS who received chlorambucil (n=11, group 1) or cyclophosphamide (n=22, group 2).


RESULTS
Age at onset of nephrosis, beginning of first and second therapy, sex ratio, duration of nephrosis before first cytotoxic therapy, interval between first and second cytotoxic therapy, number of relapses, cumulative doses of steroids and length of remission off steroids before second therapy were similar between groups. Four patients (36.4%, p<0.05) in group 1 remained in remission for a median 34.0 months, whereas only 1 patient (4.5%) in group 2 did for 53.0 months. Two patients in group 1 and 1 patient in group 2 became infrequent relapsers. Total number of nonrelapsers and infrequent relapsers was higher in group 1 (54.5%, p<0.05) than in group 2 (9.1%). Number of relapses and cumulative doses of steroids were reduced and length of remission off steroids was longer in group 1 than in group 2 (p<0.05). There was no difference between groups in frequency of side effects, and none had serious toxicity. However, the short period of follow-up in our study does not exclude the risk of azoospermia.


CONCLUSIONS
Our data suggest a superior effect of chlorambucil over cyclophosphamide in steroid-dependent and cyclophosphamide-resistant children with MCNS. A future randomized controlled clinical trial is required to confirm our findings.
Ueda
Norishi
N
Department of Developmental Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. nueda@med.nagoya-u.ac.jp
Takahashi
Kazuhiro
K
Akioka
Yuko
Y
Morooka
Masafumi
M
Ogawa
Akimasa
A
Tsuzuki
Kazuo
K
D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002699:Chlorambucil / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009402:Nephrosis, Lipoid / Q000188:drug therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D055502:Secondary Prevention; D013256:Steroids / Q000627:therapeutic use*; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D013256:Steroids; D002699:Chlorambucil; D003520:Cyclophosphamide