18

Individualised etoposide dosing allows safer dosage increases

24 patients who randomly received individualised etoposide dosing achieved a mean dose increase of 22% without a significant increase in severe leucopenia or clinically significant complications. The mean total dose was significantly higher in these patients compared with those who received etopside at a fixed dosage of 125 mg/m2/day by 72-hour infusion (459 vs 375 mg/m2). The patients had a wide range of malignancies which were refractory to conventional treatment and were stratified according to pretreatment performance status and transfusion history. Patients randomised to individualised dosing (starting dose 150 mg/m2/ day) had their doses modified according to plasma etoposide concentrations and a pharmacodynamic model to achieve a target WBC nadir of 1700/ loLL.

Mean estimated clearance for all patients was 20 ml/min/m2 (greater in dose modification compared with fixed dose group) with no relationship to body surface area. Although the mean WBC nadir was significantly lower in the dose modification group " , , the ,lIritlbility ;11

toxicity WIIS sigllijiclllltly decmuell by ;lIdMdulIl;sell dosing', and 'the mlljor bellefit WIIS the eliminllt;oll of plltients hllving intJdequate dosillg, bllSed 011 the WBeN IWBC nadir).' In addition, there does not appear to be any advantage in using pharmacokinetic variables measured during each cycle to determine dosing for subsequent cycles. ' .. , especially since intrtzpatient variability was low'. Ratain MJ. Mick R. Schilsky RL. Vogelzang NJ. Berezin F. Pharmacologically based dosing of etoposide: a means of safely increasing dose intensity. Journal of ClinIcal Oncology 9: 1480-1486. Aug 1991 81"

- 1 Nov 1991 INPHARMA® ISSN 0156-1703/91/ll01-oo18/0101.oo/0 e Adis l"terlUltio,,1Il Ltd