A Pilot Study of Protracted Topotecan Dosing Using a Pharmacokinetically Guided Dosing Approach in Children with Solid Tumors

摘要: Purpose: To assess the use of a pharmacokinetically guided topotecan strategy and evaluate toxicity protracted i.v. in children with recurrent solid tumors. Experimental design: Fifteen measurable relapsed or refractory tumors received over 30 min 5 days week for two consecutive weeks. Doses were individualized based on patient’s systemic clearance to attain single day lactone area under plasma concentration time curve (AUC) 120–180 ng/ml × h (cohort 1) 80–120 2). Clinical responses assessed by standard criteria. Results: Twenty-nine courses administered, 11 cohort 1 18 2. The median dosages required achieve target AUCs cohorts 2 4 mg/m (range, 2.6–6) 3 2.6–4.2), respectively. intersubject variance exceeded intrasubject 2-fold. With pharmacokinetic targeting approach, we observed that 78% (46 59) measured AUC values within range. number an absolute neutrophil count ≥500/mm was similar between cohorts; however, febrile neutropenia serious infections limited our ability deliver drug needed secure higher exposure 1). Five partial observed. Conclusion: Protracted dosing using possible this heavily pretreated group children.