Phase I trial and pharmacokinetic (PK) study of satraplatin in children and young adults with refractory solid tumors including brain tumors.

2554 Background: Satraplatin is an orally bioavailable platinum analog. Based on pre-clinical activity (IC500.02-8 µg/ml) including activity in cisplatin resistant cell lines, and clinical activity without neuro-, nephro-, or ototoxicity in adults with refractory tumors, we developed a phase 1 trial to determine the toxicities, maximum tolerated dose (MTD), and PKs of satraplatin in children with refractory solid tumors. Methods: Satraplatin (10 and 50 mg capsules) was administered orally once daily on days 1 - 5 of a 28 day cycle to cohorts of 3-6 patients (pts) at 60 mg/m2/dose (DL 1) and 80 mg/m2/dose (DL 2). Plasma ultrafiltrate (PUF) platinum was measured using atomic absorption spectroscopy during cycle 1 for PK analysis. Results: 9 pts [5 male, 4 female, median age 17 years (range 8-19)] with malignant glioma (n=4), ependymoma (n=2), medulloblastoma (n=1), osteosarcoma (n=1), or hepatoblastoma (n=1) received 1-10+ cycles (median 2). The MTD was exceeded at DL 2 as 2/4 pts had dose limiting toxiciti...