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.
|Number of pages||8|
|Journal||European Journal of Cancer|
|State||Published - Jun 2020|
Bibliographical noteFunding Information:
This work was supported in part by Cancer Center Grant CA23099 and Cancer Center Support CORE Grant P30 CA 21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities .
This work was supported in part by Cancer Center Grant CA23099 and Cancer Center Support CORE Grant P30 CA 21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities.
© 2020 Elsevier Ltd
- Phase I
- Solid tumours
ASJC Scopus subject areas
- Cancer Research