Pilot study of the novel chemotherapy regimen of topotecan, ifosfamide, and carboplatin (TIC) in children with refractory/recurrent solid tumors.

9545 Background: The combination of ifosfamide, carboplatin, and etoposide (ICE) has previously been demonstrated to be an effective regimen in children with recurrent or refractory solid tumors (Cairo et al JPHO, 2001). Substituting topotecan (a Topoisomerase I inhibitor) for etoposide (a Topoisomerase II inhibitor) may be a more efficacious regimen due to the cytotoxic activity of topotecan in pediatric solid tumor xenografts, as well as its in vitro synergistic activity with platinum and alkylating agents (Houghton et al CCP, 1992). Methods: In this limited institution study, we evaluated the addition of escalating doses of topotecan with fixed doses of ifosfamide and carboplatin. Patients initially received ifosfamide 3,000 mg/m2/day × 3 days, carboplatin dosed to an AUC of 3 mg/ml/min (equivalent to 250 mg/m2/dose) × 3 days, and topotecan × 3 days. 6 patients were enrolled at dose level #1 (topotecan: 0.5 mg/m2/day), with 2 patients having ifosfamide related neurotoxicity (related to the dosing sched...