Phase I study of bevacizumab plus irinotecan in pediatric patients with recurrent/refractory solid tumors

Jpn J Clin Oncol. 2013 Nov;43(11):1073-9. doi: 10.1093/jjco/hyt124. Epub 2013 Sep 3.


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).

Keywords: Phase I; bevacizumab; irinotecan; solid tumors.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Bevacizumab
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Central Nervous System Neoplasms / drug therapy*
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Ependymoma / drug therapy
  • Female
  • Glioma / drug therapy
  • Humans
  • Irinotecan
  • Male
  • Maximum Tolerated Dose*
  • Medulloblastoma / drug therapy
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasms / drug therapy
  • Rhabdomyosarcoma / drug therapy
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Irinotecan
  • Camptothecin