Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma.
Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma.
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DOI：
10.1093/oncolo/oyac003
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发表时间：
2022-08-05
期刊：
影响因子：
5.8
通讯作者：
Kim, Richard
中科院分区：
文献类型：
--
作者：
Mehta, Rutika;Frakes, Jessica;Kim, Jongphil;Nixon, Andrew;Liu, Yingmiao;Howard, Lauren;Jimenez, Maria E. Martinez;Carballido, Estrella;Imanirad, Iman;Sanchez, Julian;Dessureault, Sophie;Xie, Hao;Felder, Seth;Sahin, Ibrahim;Hoffe, Sarah;Malafa, Mokenge;Kim, Richard
氟嘧啶新辅助放化疗后手术和辅助化疗多年来一直是局部晚期II期和III期直肠癌的标准治疗方法。有较高的疾病复发风险；因此，优化放化疗策略仍然是一个未满足的需求。基于一些研究，有证据表明VEGF/PDGFR阻断与放疗有协同作用。在这个I期剂量递增和剂量扩展研究中，我们研究了3种不同剂量水平的lenvatinib联合卡培他滨放化疗治疗局部晚期直肠癌。共纳入20例患者，其中19例符合疗效评估条件。联合用药耐受性良好，MTD为24mg lenvatinib。该队列和pCR的降期率分别为84.2%和37.8%。基于血液的蛋白质生物标志物TSP-2、VEGF- r3和VEGF与NAR评分相关，并且在反应类别之间也存在差异表达。NAR，即新辅助直肠评分，包括cT临床肿瘤分期、pT病理肿瘤分期和pN病理淋巴结分期，为评估临床试验结果提供了一个连续的变量。lenvatinib联合卡培他滨和放射治疗局部晚期直肠癌是安全且耐受的，并确定了潜在的基于血液的生物标志物。在这项I期剂量递增和剂量扩展研究中，研究了三种不同剂量水平的lenvatinib联合卡培他滨放化疗治疗局部晚期直肠癌。
Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. NCT02935309 In this phase I dose escalation and dose expansion study, three different dose levels of lenvatinib, in combination with capecitabine-based chemoradiation for locally advanced rectal cancer, were studied.
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影响因子：
3.8
作者：
Salazar R;Capdevila J;Laquente B;Manzano JL;Pericay C;Villacampa MM;López C;Losa F;Safont MJ;Gómez A;Alonso V;Escudero P;Gallego J;Sastre J;Grávalos C;Biondo S;Palacios A;Aranda E
通讯作者：
Aranda E
影响因子：
45.3
作者：
Dewdney, Alice;Cunningham, David;Chau, Ian
通讯作者：
Chau, Ian
影响因子：
51.1
作者：
Roedel, Claus;Graeven, Ullrich;Seipelt, G.
通讯作者：
Seipelt, G.
影响因子：
45.3
作者：
Gerard, Jean-Pierre;Azria, David;Conroy, Thierry
通讯作者：
Conroy, Thierry
影响因子：
158.5
作者：
Bosset, Jean-Francois;Collette, Laurence;Ollier, Jean-Claude
通讯作者：
Ollier, Jean-Claude