title: Phase I and pharmacokinetic study of thalidomide with carboplatin in children with cancer.
abstract: OBJECTIVE
  Tumor growth and metastasis is believed to depend on the tumor's ability to induce neovascularization. Recent studies have indicated that thalidomide inhibits angiogenesis. We performed a phase I and pharmacokinetic study of thalidomide with carboplatin in children with refractory solid tumors.
  
  
  METHODS
  Carboplatin was administered as a single intravenous dose once every 21 days at a target area under the concentration-time curve of 6 mg/mL.min. Thalidomide was administered daily by mouth. The initial dose level was 100 mg/m(2)/d with intrapatient dose escalation to a maximum dose of 300 mg/m(2)/d. The next cohort of patients started at a dose of 300 mg/m(2)/d, with intrapatient dose escalation to a maximum dose of 500 mg/m(2)/d. Standard response and adverse event criteria were used. Serial blood samples for thalidomide pharmacokinetics studies were obtained after the first dose.
  
  
  RESULTS
  Twenty-two patients received 56 cycles of therapy. The maximum tolerated thalidomide dose was 400 mg/m(2)/d. The dose-limiting toxicity was somnolence. There were no objective responses. Thalidomide's apparent clearance was 55 +/- 16 mL/min/m(2) and the terminal half-life was 5.9 +/- 2.8 hours. There was no evidence of dose-dependent pharmacokinetics in the narrow range studied.
  
  
  CONCLUSIONS
  Thalidomide at a dose of 400 mg/m(2)/d can be safely administered to children with solid tumors in combination with carboplatin. Somnolence is the major toxicity. In addition, we have characterized the pharmacokinetic behavior of thalidomide in children. This study can serve as the basis for future investigation of thalidomide as an anticancer agent in children.
authors.affiliation: Texas Children's Cancer Center, 6621 Fannin, MC 3-3320, Houston, TX 77030, USA. sberg@txccc.org
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Bomgaars
authors.forename: Aleksander
authors.initials: A
authors.lastname: Aleksic
authors.forename: John F
authors.initials: JF
authors.lastname: Kuttesch
authors.forename: Renee A
authors.initials: RA
authors.lastname: Klenke
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Berg
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D016190:Carboplatin