Implementing Good Clinical Practice in two noncommercial phase II studies in children with cancer.

Background: In noncommercial clinical drug research the implementation of the principles of Good Clinical Practice (GCP) has been criticized for introducing unnecessary bureaucracy at the expense of scientific activity, especially when small populations such as children or patients with orphan diseases are concerned.

Patients And Methods: From May 2003 to September 2005, we conducted two prospective open-label multicenter phase II studies in pediatric oncology. Aside from medical questions, these studies set out to explore the requirements according to the essential standards of the ICH-GCP Guideline in anticipation of the implementation of the EU Regulation in German Drug Law in August 2004; the latter, prospective investigation was initiated by the Coordinating Center for Clinical Trials (KKS).

Phase II study of gemcitabine in children with solid tumors of mesenchymal and embryonic origin.

The therapeutic benefit and side-effect profile of gemcitabine in adults with relapsed solid tumors is well known. So far, few data are available about its significance in pediatric relapsed solid tumors. To determine the efficacy and tolerability of gemcitabine in children, the drug was administered by intravenous short-term infusion over 30 min at a dose of 1200 mg/m2 weekly for 3 weeks as one cycle in children with relapsed solid tumor of embryonic or mesenchymal origin.

Population pharmacokinetics of low-dose paclitaxel in patients with brain tumors.

Our aim was to assess the pharmacokinetics of a low-dose schedule of paclitaxel in combination with radiation therapy in patients with brain tumors. Eighteen patients received 20-50 mg/m2 paclitaxel as a 1-h infusion 18-24 h before radiation with 2 Gy on 5 consecutive days. In total, 156 plasma samples from 13 patients and 38 urine samples from nine patients were collected and analyzed by a validated capillary electrophoresis method.

Pharmacology of all-trans-retinoic acid in children with acute promyelocytic leukemia.

Background: Due to severe side effects in virtually all children treated with a standard dose of 45 mg/m(2)/day all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) the AML-BFM study group reduced the dosage to 25 mg/m(2)/day. For the lack of data on the use of ATRA at this dosage in children with APL, the study group further decided to evaluate the pharmacokinetics and metabolism of ATRA in children.

Procedure: Twenty-three pharmacokinetic and metabolic profiles of ATRA were studied in 14 children (aged 0.