A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy.

Autor: Navid F; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN., Santana VM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN., Neel M; Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN., McCarville MB; Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN.; Department of Radiology, University of Tennessee Health Science Center, Memphis, TN., Shulkin BL; Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN.; Department of Radiology, University of Tennessee Health Science Center, Memphis, TN., Wu J; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN., Billups CA; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN., Mao S; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN., Daryani VM; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN., Stewart CF; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN., Kunkel M; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN., Smith W; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN., Ward D; Department of Pharmaceutical Services, St. Jude Children's Research Hospital, Memphis, TN., Pappo AS; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN., Bahrami A; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN., Loeb DM; Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD., Reikes Willert J; Pediatric Hematology/Oncology/Blood and Marrow Transplant, Rady Children's Hospital, San Diego, CA., Rao BN; Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN.; Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN., Daw NC; Division of Pediatrics, MD Anderson Cancer Center, Houston, TX.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2017 Oct 01; Vol. 141 (7), pp. 1469-1477. Date of Electronic Publication: 2017 Jul 03.
DOI: 10.1002/ijc.30841
Abstrakt: Increased vascular endothelial growth factor (VEGF) expression in osteosarcoma correlates with a poor outcome. We conducted a phase II trial to evaluate the feasibility and efficacy of combining bevacizumab, a monoclonal antibody against VEGF, with methotrexate, doxorubicin and cisplatin (MAP) in patients with localized osteosarcoma. Eligible patients received two courses of MAP chemotherapy before definitive surgery at week 10. Bevacizumab (15 mg/kg) was administered 3 days before starting chemotherapy then on day 1 of weeks 3 and 5 of chemotherapy. After surgery, patients received MAP for a total of 29 weeks; bevacizumab was added every 2 or 3 weeks on day 1 of chemotherapy at least 5 weeks after surgery. Group sequential monitoring rules were used to monitor for unacceptable bevacizumab-related targeted toxicity (grade 4 hypertension, proteinuria or bleeding, grade 3 or 4 thrombosis/embolism, and grade 2-4 major wound complications). Thirty-one patients (median age 12.8 years) with localized osteosarcoma were enrolled. No unacceptable targeted toxicities were observed except for wound complications (9 minor and 6 major), which occurred in 15 patients; none required removal of prosthetic hardware or amputation. The estimated 4-year event-free survival (EFS) rate and overall survival rate were 57.5 ± 10.0% and 83.4 ± 7.8%, respectively. Eight (28%) of 29 evaluable patients had good histologic response (<5% viable tumor) to preoperative chemotherapy. The addition of bevacizumab to MAP for localized osteosarcoma is feasible but frequent wound complications are encountered. The observed histologic response and EFS do not support further evaluation of bevacizumab in osteosarcoma.
(© 2017 UICC.)
Databáze: MEDLINE
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