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

作者：Navid Fariba^*; Santana Victor M; Neel Michael; McCarville M Beth; Shulkin Barry L; Wu Jianrong; Billups Catherine A; Mao Shenghua; Daryani Vinay M; Stewart Clinton F; Kunkel Michelle; Smith Wendene; Ward Deborah; Pappo Alberto S; Bahrami Armita; Loeb David M; Willert Jennifer Reikes; Rao Bhaskar N; Daw Najat C

来源：International Journal of Cancer, 2017, 141(7): 1469-1477.

DOI：10.1002/ijc.30841

• osteosarcoma
• bevacizumab
• chemotherapy
• wound healing
• phase II
• survival

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.

• 出版日期2017-10-1