■患有复发性和转移性实体瘤的儿童和青少年预后较差。先前的1期研究(ANGIO1)用贝伐单抗靶向血管生成,索拉非尼,和环磷酰胺,在一部分患者中表现出活动信号。在这里,我们报告了以推荐的2期剂量治疗的一组儿科和年轻成年患者的结果。
■回顾了接受ANGIO1治疗的难治性或复发性实体瘤患者的电子病历。治疗周期持续21天,包括贝伐单抗,索拉非尼,和环磷酰胺.使用不良事件通用术语标准评估毒性,v5.0.使用实体瘤中的反应评价标准(RECIST1.1)评价反应。
■39名患者(22名男性,17名女性;中位年龄15岁;范围1-22岁)接受治疗方案。最常见的诊断包括骨肉瘤(n=21;14尤因肉瘤,7个骨肉瘤)和软组织肉瘤(n=9;2个横纹肌肉瘤,3滑膜肉瘤,2个促纤维增生性小圆细胞肿瘤,和2个高级别肉瘤)。最常见的3级非血液学毒性包括高血压(2,5.4%)和血尿(2,5.4%)。5例患者(13.5%)有气胸(3例在进行性疾病,1肺活检后,和1自发)。常见的3/4级血液学毒性为淋巴细胞减少症(19,51%)和白细胞减少症(13,35%)。16例患者(43.2%)出现了2级或以下的掌-足红感觉障碍。总共施用297个周期。23名患者需要减少环磷酰胺的剂量,治疗期间索拉非尼或贝伐单抗,所有患者在调整剂量后仍能获得临床获益.1例患者(尤因肉瘤)在11个周期后达到完全缓解;2例患者(尤因肉瘤,高级别肉瘤)分别在第2和第4周期后获得部分缓解,并且有20例患者的疾病稳定为最佳缓解。
■静脉注射贝伐单抗联合口服索拉非尼和节拍环磷酰胺是耐受的,需要最少的支持治疗或额外的临床就诊。在超过一半的治疗患者中观察到疾病长时间稳定。骨肉瘤患者表现出活动信号,表明在前期设置中纳入治疗作为维持方案可能有益,或作为姑息治疗方案。
UNASSIGNED: Children and adolescents with recurrent and metastatic solid tumors have a poor outcome. A previous phase 1 study (ANGIO1) targeting angiogenesis with bevacizumab, sorafenib, and cyclophosphamide, demonstrated a signal of activity in a subset of patients. Here we report the results of a cohort of pediatric and young adult patients treated at the recommended phase 2 doses.
UNASSIGNED: Electronic medical records of patients with refractory or recurrent solid tumors who received ANGIO1 therapy were reviewed. Treatment cycles lasted 21 days and included bevacizumab, sorafenib, and cyclophosphamide. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v5.0. Responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST1.1).
UNASSIGNED: Thirty-nine patients (22 male, 17 female; median age 15 years; range 1-22 years) received the treatment regimen. The most common diagnoses included bone sarcomas (n=21; 14 Ewing sarcoma, 7 osteosarcoma) and soft tissue sarcomas (n=9; 2 rhabdomyosarcoma, 3 synovial sarcoma, 2 desmoplastic small round cell tumors, and 2 high-grade sarcoma). The most common Grade 3 non-hematologic toxicities included hypertension (2, 5.4%) and hematuria (2, 5.4%). Five patients (13.5%) had a pneumothorax (3 at progressive disease, 1 post lung biopsy, and 1 spontaneous). Common Grade 3/4 hematologic toxicities were lymphopenia (19, 51%) and leukopenia (13, 35%). Sixteen patients (43.2%) developed palmar-plantar erythrodysesthesia Grade 2 or less. A total of 297 cycles were administered. Twenty-three patients required a dose reduction of cyclophosphamide, sorafenib or bevacizumab during therapy, all of whom continued to have clinical benefit following dose modification. One patient (Ewing sarcoma) achieved a complete response after 11 cycles; 2 patients (Ewing sarcoma, high grade sarcoma) achieved a partial response following cycles 2 and 4, respectively and 20 patients had stable disease as a best response.
UNASSIGNED: Intravenous bevacizumab combined with oral sorafenib and metronomic cyclophosphamide was tolerated and required minimal supportive care or additional clinic visits. Disease stabilization for prolonged time periods was observed in greater than half of the treated patients. Patients with bone sarcoma demonstrated a signal of activity suggesting possible benefit from incorporation of the therapy as a maintenance regimen in upfront setting, or as a palliative regimen.