title: 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.
abstract: Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase 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 days with a starting dose of 150 mg/m2 and an escalation to 185 mg/m2 and 235 mg/m2 in subsequent patient cohorts. G-CSF (5 microg/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the post-nadir neutrophil count reached 10,000/microl. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m2. Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/1microl) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/microl), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related 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/m2, which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85 % higher than the recommended adult dose.
authors.affiliation: Department of Hematology Oncology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC 20010, USA. nseibel@cnmc.org
authors.forename: N L
authors.initials: NL
authors.lastname: Seibel
authors.forename: S M
authors.initials: SM
authors.lastname: Blaney
authors.forename: M
authors.initials: M
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Krailo
authors.forename: R
authors.initials: R
authors.lastname: Hutchinson
authors.forename: R B
authors.initials: RB
authors.lastname: Mosher
authors.forename: F M
authors.initials: FM
authors.lastname: Balis
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011994:Recombinant Proteins; D043823:Taxoids
chemical_list: D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D017239:Paclitaxel; D000069585:Filgrastim