瑞戈非尼
医学
伊立替康
横纹肌肉瘤
内科学
长春新碱
白细胞减少症
耐火材料(行星科学)
中性粒细胞减少症
进行性疾病
不利影响
胃肠病学
外科
癌症
化疗
肉瘤
结直肠癌
病理
环磷酰胺
物理
天体生物学
作者
Michela Casanova,Francisco Bautista,Quentin Campbell-Hewson,Guy Makin,Lynley V. Marshall,Arnauld Verschuur,Adela Cañete Nieto,Nadège Corradini,Bart A. Ploeger,Barbara J. Brennan,Udo Mueller,Henry Gong,Jonathan Chung,Birgit Geoerger
标识
DOI:10.1158/1078-0432.ccr-23-0257
摘要
This phase Ib study defined the safety, MTD, and recommended phase II dose (RP2D) of regorafenib combined with vincristine and irinotecan (VI). Secondary objectives were evaluation of antitumor activity and pharmacokinetics (PK) of regorafenib and irinotecan.Patients aged 6 months to <18 years with relapsed/refractory solid malignancies [≥50% with rhabdomyosarcoma (RMS)] received regorafenib (starting dose 72 mg/m2/day) concomitantly or sequentially with vincristine 1.5 mg/m2 on days 1 and 8, and irinotecan 50 mg/m2 on days 1-5 (21-day cycle). Adverse events (AE) and tumor response were assessed. PK (regorafenib and irinotecan) were evaluated using a population PK model.We enrolled 21 patients [median age, 10 years; 12, RMS; 5, Ewing sarcoma (EWS)]. The MTD/RP2D of regorafenib in the sequential schedule was 82 mg/m2. The concomitant dosing schedule was discontinued because of dose-limiting toxicities in 2 of 2 patients treated. Most common grade 3/4 (>30% of patients) AEs were neutropenia, anemia, thrombocytopenia, and leukopenia. The overall response rate was 48% and disease control rate [complete response (CR)/partial response/stable disease/non-CR/non-progressive disease] was 86%. Median progression-free survival was 7.0 months [95% confidence interval (CI), 2.9-14.8] and median overall survival was 8.7 months (95% CI, 5.5-16.3). When combined with VI, regorafenib PK was similar to single-agent PK in children and adults (treated with regorafenib 160 mg/day).Regorafenib can be combined sequentially with standard dose VI in pediatric patients with relapsed/refractory solid tumors with appropriate dose modifications. Clinical activity was observed in patients with RMS and EWS (ClinicalTrials.gov NCT02085148).
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