PHASE-I TRIAL OF DOCETAXEL ADMINISTERED AS A 1-HOUR INFUSION IN CHILDREN WITH REFRACTORY SOLID TUMORS - A COLLABORATIVE PEDIATRIC BRANCH, NATIONAL-CANCER-INSTITUTE AND CHILDRENS CANCER GROUP TRIAL

Purpose: A phase I trial of docetaxel wets performed to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities, and the in cidence and severity of other toxicities in children with refractory s olid tumors. Patients and Methods: Forty-four children received 103 co urses of docetaxel administered as a 1-hour intravenous infusion every 21 days. Doses ranged from 55 to 150 mg/m(2). MTD was defined in heav ily pretreated and less heavily pretreated (less than or equal to 2 pr ior chemotherapy regimens, no prior bone marrow transplantation [BMT], and no radiation to the spine, skull, ribs, or pelvic bones) patients . Results: Dose-related neutropenia was the primary dose-limiting toxi city. The MTD in the heavily pretreated patient group was 65 mg/m(2), but the less heavily pretreated patients tolerated a significantly hig her dose of docetaxel (maximum-tolerated dose, 125 mg/m(2)). Neutropen ia and constitutional symptoms consisting of malaise, myalgias, and an orexia were the dose-limiting toxicities at 150 mg/m(2) in the less he avily pretreated patients. Thrombocytopenia was not prominent, even in patients who experienced dose-limiting neutropenia. Common nonhematol ogic toxicities of docetaxel included skin rashes, mucositis, and mild elevations of serum transaminases. Neuropathy was uncommon, Periphera l edema and weight gain were observed in two of five patients who rece ived more than three cycles of docetaxel. A complete response [CR] was observed in one patient with rhabdomyosarcoma, a partial response (PR ) in one patient with peripheral primitive neuroectodermal tumor (PPNE T), and a minimal response (MR) in two patients with PPNET. Three of t he four responding patients were treated at doses greater than or equa l to 100 mg/m2. Conclusion: The recommended phase II dose of docetaxel administered as a 1-hour intravenous infusion in children with solid tumors is 125 mg/m(2). Because neutropenia was the dose-limiting toxic ity and thrombocytopenia was mild, further escalation of the dose shou ld be attempted with granulocyte colony-stimulating factor (G-CSF) sup port. (C) 1997 by American Society of Clinical Oncology.