Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: A collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial

Neutropenia is the dose-limiting toxicity of docetaxel in children. This Ph ase I trial was designed to determine the maximum tolerated dose, the dose- limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v, infusion for 1 h every 21 da ys with a starting dose of 150 mg/m(2) and an escalation to 185 mg/m(2) and 235 mg/m(2) in subsequent patient cohorts. G-CSF (5 mu g/kg/day) was admin istered s.c., starting 48 h after docetaxel and continuing until the postna dir neutrophil count reached 10,000/mu l. Seventeen patients received 27 co urses of docetaxel with G-CSF support. Generalized erythematous desquamatin g skin rash and myalgias were dose-limiting at 235 mg/m(2). Localized and g eneralized rashes were seen at all of the three dose levels. Neutropenia (m edian nadir, 95/mu l) occurred at all of the dose levels but was brief in d uration and not dose-limiting. Thrombocytopenia was minimal (median platele t count nadir, 139,000/mu l), and the severity of neutropenia and thrombocy topenia did not seem to be related to the docetaxel dose. Other docetaxel-r elated toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis , back pain, asthenia, and neuropathy, One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G- CSF support in children is 185 mg/m(2), which is 50% higher than the maximu m tolerated dose of docetaxel alone in children and 85% higher than the rec ommended adult dose.