Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours

Sara M. Federico, Kenneth J. Caldwell, Mary B. McCarville, Vinay M. Daryani, Clinton F. Stewart, Shenghua Mao, Jianrong Wu, Andrew M. Davidoff, Victor M. Santana, Wayne L. Furman, Alberto S. Pappo, Fariba Navid

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Angiogenesis is critical for tumour growth and metastasis. Dual inhibition of vascular endothelial growth factors and platelet-derived growth factor receptors suppresses angiogenesis. This expansion cohort of a phase I study targeted angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with recurrent solid tumours. Methods: An expansion cohort including patients with refractory or recurrent solid tumours was enrolled and received bevacizumab (15 mg/kg IV, day 1), sorafenib (90 mg/m2 po twice daily, days 1–21) and low-dose cyclophosphamide (50 mg/m2 po daily, days 1–21). Each course was 21 days. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v3.0, and responses were evaluated by Response Evaluation Criteria in Solid Tumors criteria. Serial bevacizumab pharmacokinetic (PK) studies were performed during course 1. Results: Twenty-four patients (15 males; median age 14.5 yrs; range 1–22 yr) received a median of 6 courses (range 1–18). Twelve patients had a bone or soft tissue sarcoma. The most common grade III/IV non-haematologic toxicities were hypertension (N = 4), hand/foot rash (N = 3) and elevated lipase (N = 3). The most common grade III/IV haematologic toxicities were neutropenia (N = 7) and lymphopenia (N = 17). Three patients (2 synovial sarcoma, 1 rhabdoid tumour) achieved a partial response and 18 had stable disease. The progression-free survival at 3 and 6 months were 78.1% (95% confidence interval [CI] 60.6–95.6%) and 54% (95% CI 30.2–78.2%), respectively. Bevacizumab PKs in 15 patients was similar to published adult PK results. Conclusions: Intravenous bevacizumab combined with oral sorafenib and low-dose cyclophosphamide was tolerated and demonstrated promising activity in a subset of childhood solid tumours.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalEuropean Journal of Cancer
Volume132
DOIs
StatePublished - Jun 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Bevacizumab
  • Cyclophosphamide
  • Paediatric
  • Phase I
  • Solid tumours
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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