The oncologist | |
Anlotinib, Vincristine, and Irinotecan for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy: A Two-Cohort, Phase Ib/II Trial | |
article | |
Jie Xu1  Lu Xie1  Xin Sun1  Kuisheng Liu1  Xiaodong Tang1  Taiqiang Yan1  Rongli Yang1  Wei Guo1  Jin Gu2  | |
[1] Musculoskeletal Tumor Center, Peking University People's Hospital;Department of Gastrointestinal Surgery, Peking University Shougang Hospital | |
关键词: Anlotinib; Irinotecan; Ewing sarcoma; | |
DOI : 10.1002/onco.13726 | |
学科分类:地质学 | |
来源: AlphaMed Press Incorporated | |
【 摘 要 】
Background Both protracted irinotecan and antiangiogenesis therapy have shown promising efficacy against Ewing sarcoma (EWS). Methods Patients diagnosed with recurrent or refractory EWS were enrolled and further categorized into cohort A (≥16 years) or cohort B (<16 years). In the dose-defining phase Ib portion, anlotinib was given daily at a fixed dose, while a 3+3 design with dose de-escalation was used to determine the dose of irinotecan. The next dose-expanding phase II portion employed a conventional two-stage study design model. The primary endpoint was objective response rate at 12 weeks (ORR 12w ). Results A total of 41 patients finally received the treatment regimen, including 29 in cohort A and 12 in cohort B. For cohort A, the first five patients were treated at the initial level of 20 mg/m 2 /d d × 5 × 2, and two of them subsequently a dose-limiting toxicity (DLT). An additional six patients were then treated at 15 mg/m 2 without any DLT, and the RP2D was determined. Notably, 23 out of 24 patients in cohort A were available for response evaluation at 12 weeks. ORR 12w was determined to be 62.5%. For cohort B, no DLT was observed in the first six patients at the initial dose level. At last, 12 patients were included in cohort B. The ORR 12w was 83.3%. The most frequently observed grade 3/4 adverse events were leukopenia (28.5%), neutropenia (24.4%), anemia (8.7%), and diarrhea (3.7%). Conclusion The combination of vincristine, irinotecan, and anlotinib demonstrated an acceptable toxicity profile and promising clinical efficacy in patients with advanced EWS. Implications for Practice This is the first trial to evaluate an irinotecan-based regimen in combination with antiangiogenesis tyrosine kinase inhibitors in Ewing sarcoma (EWS). A 3+3 design with dose de-escalation was used to determine the most appropriate dose of irinotecan in each cohort. The next dose-expanding phase II portion employed a conventional two-stage study design model. The objective response rate was 62.5% for adults and 83.3% for children. Median overall survival was not matured. This study shows that the combination of vincristine, irinotecan, and anlotinib demonstrates an acceptable toxicity profile and promising clinical efficacy in patients with advanced EWS.
【 授权许可】
CC BY|CC BY-NC
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202108130001069ZK.pdf | 564KB | download |