title: Phase I study of bevacizumab plus irinotecan in pediatric patients with recurrent/refractory solid tumors.
abstract: OBJECTIVE
  Studies have suggested that bevacizumab has shown activity against various pediatric solid tumors. We, therefore, conducted a Phase I study of bevacizumab plus irinotecan in Japanese children with recurrent, progressive or refractory solid tumors.
  
  
  METHODS
  The starting dose was bevacizumab 10 mg/kg over 60-90 min and irinotecan 125 mg/m(2) over 90 min intravenously on Days 1, 15 and 29. The dose of irinotecan was 340 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs. Treatment was repeated every 6 weeks for up to three courses in the absence of disease progression or unacceptable toxicity.
  
  
  RESULTS
  Of 11 patients, 9 (median age, 9 years) were fully assessable for toxicity and received 24 courses. Dose-limiting toxicities were Grade 2 diarrhea and Grade 4 neutropenia/thrombocytopenia in two of the five patients at dose level 1. No dose-limiting toxicities were observed in four patients at dose level -1 at bevacizumab 10 mg/kg and irinotecan 100 mg/m(2) (270 mg/m(2) for patients taking enzyme-inducing antiepileptic drugs). The maximum-tolerated dose was bevacizumab 10 mg/kg and irinotecan 100 mg/m(2). The most frequent non-dose-limiting toxicities were Grade 1 or 2 hypertension, bleeding and hematologic toxicity. One patient with optic nerve glioma had a partial response. Three patients with medulloblastoma, optic nerve glioma and diffuse intrinsic pontine glioma had stable disease.
  
  
  CONCLUSIONS
  Combination chemotherapy of bevacizumab plus irinotecan was well tolerated in children. We plan Phase II pediatric studies at doses of bevacizumab 10 mg/kg and irinotecan 100 mg/m(2) every 2 weeks (270 mg/m(2) for patients taking enzyme-inducing antiepileptic drugs).
authors.affiliation: *2-13-22 Miyakojima-Hondori, Miyakojima-ku, Osaka 534-0021, Japan. keik-okada@hospital.city.osaka.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Okada
authors.forename: Kai
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Chika
authors.initials: C
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujisaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Osugi
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004806:Ependymoma / Q000188:drug therapy; D005260:Female; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008527:Medulloblastoma / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin
keywords: Phase I; bevacizumab; irinotecan; solid tumors