r therapy DRUG THERAPY FOR CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME Chlorambucil-prednisone combo shows long term effectiveness The long term effects of a 5- to IS-week course of chlorambucil and prednisone were evaluated in 59 children with idiopathic nephrotic syndrome. The children had previously received prednisone alone and had had frequent relapses or steroid dependency or resistance. 65 courses of dual therapy were followed up for 1-12 years (mean,S). 95% of patients were in remission at I year, and 85 % at 4 years. All but 2 had remissions lasting longer than those induced by steroids alone, and only 8 others had I or more relapses after therapy. Life-table analysis of 2 dosage schedules of chlorambucil at 4 years showed that 91 % of patients on low doses { < O. 3mg/kg) and 80 % ofthose on high doses ( ;;. 3.0mg/kg) were still in remission. It seems that prolonged use of chlorambucil in daily doses above O.3mg/kg/day or cumulative doses above 14mg/kg may no longer be warranted. Williams. S.A. et al. : New England Journal of Medicine 302: 929 (24 Apr 19 80) ... but chlorambucil should be used with caution only in difficult cases Despite the apparent therapeutic effectiveness of chlorambucil in childhood nephrosis, there is still a need for great caution in the use of the drug. Although short term toxicity appears to be less frequent with chlorambucil than with other alkylating agents, especially when it is given in the low-dose regimen described by Williams et al., the long term effects may turn out to be disastrous. Some of the criteria proposed by Williams et al. for the use of chlorambucil in these patients may have been unacceptable. The presence of small amounts of protein in a 24-hour urine sample is abnormal but may be of little clinical. importance. Few physicians would be moved to use the potentially dangerous chlorambucil for treating proteinuria exceeding I OOmg/day, the level considered as a criterion indicating 'relapses' or 'steroid dependence,' and the need for this drug. Lastly, and most importantly, a majority of the patients in the study received doses of chlorambucil larger than those that have been associated with the appearance ofleukemia in later life. For this reason, it is suggested that the exposure of children to the long term hazards of chlorambucil can be justified only in those with serious steroid toxicity. such as uncontrollable hyPertension, severe diabetes mellitus, significant growth retardation and disabling emotional disorders . . Lewis, EJ. : New England Journal of Medicine 30 2: 96 3 (24 Apr 1980) 0156-2703/80/ 0510-0009 $00.50/0 ©ADIS Press INPHARMA 10 May 1980 9

DRUG THERAPY FOR CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME

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DRUG THERAPY FOR CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME

Chlorambucil-prednisone combo shows long term effectiveness The long term effects of a 5- to IS-week course of chlorambucil and prednisone were evaluated in 59 children with idiopathic nephrotic syndrome. The children had previously received prednisone alone and had had frequent relapses or steroid dependency or resistance. 65 courses of dual therapy were followed up for 1-12 years (mean,S). 95% of patients were in remission at I year, and 85 % at 4 years. All but 2 had remissions lasting longer than those induced by steroids alone, and only 8 others had I or more relapses after therapy. Life-table analysis of 2 dosage schedules of chlorambucil at 4 years showed that 91 % of patients on low doses { < O.3mg/kg) and 80 % ofthose on high doses ( ;;. 3.0mg/kg) were still in remission. It seems that prolonged use of chlorambucil in daily doses above O.3mg/kg/day or cumulative doses above 14mg/kg may no longer be warranted. Williams. S.A. et al. : New England Journal of Medicine 302: 929 (24 Apr 1980)

... but chlorambucil should be used with caution only in difficult cases Despite the apparent therapeutic effectiveness of chlorambucil in childhood nephrosis, there is still a need for great caution in the use of the drug. Although short term toxicity appears to be less frequent with chlorambucil than with other alkylating agents, especially when it is given in the low-dose regimen described by Williams et al., the long term effects may turn out to be

disastrous. Some of the criteria proposed by Williams et al. for the use of chlorambucil in these patients may have been unacceptable. The presence of small amounts of protein in a 24-hour urine sample is abnormal but may be of little clinical. importance. Few physicians would be moved to use the potentially dangerous chlorambucil for treating proteinuria exceeding I OOmg/day, the level considered as a criterion indicating 'relapses' or 'steroid dependence,' and the need for this drug. Lastly, and most importantly, a majority of the patients in the study received doses of chlorambucil larger than those that have been associated with the appearance ofleukemia in later life. For this reason, it is suggested that the exposure of children to the long term hazards of chlorambucil can be justified only in those with serious steroid toxicity. such as uncontrollable hyPertension, severe diabetes mellitus, significant growth retardation and disabling emotional disorders . . Lewis, EJ. : New England Journal of Medicine 302: 96 3 (24 Apr 1980)

0156-2703/80/ 0510-0009 $00.50/0 ©ADIS Press INPHARMA 10 May 1980 9