The combination of axitinib followed by paclitaxel/carboplatin yields extended survival in advanced BRAF wild-type melanoma: results of a clinical/correlative prospective phase II clinical trial.
The combination of axitinib followed by paclitaxel/carboplatin yields extended survival in advanced BRAF wild-type melanoma: results of a clinical/correlative prospective phase II clinical trial.
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DOI：
10.1038/bjc.2014.541
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发表时间：
2015-04-14
影响因子：
8.8
通讯作者：
Daud, A. I.
中科院分区：
文献类型：
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作者：
Algazi, A. P.;Cha, E.;Ortiz-Urda, S. M.;McCalmont, T.;Bastian, B. C.;Hwang, J.;Pampaloni, M. H.;Behr, S.;Chong, K.;Cortez, B.;Quiroz, A.;Coakley, F.;Liu, S.;Daud, A. I.
在晚期黑色素瘤中，同时化疗和抑制血管内皮生长因子(VEGF)并没有显示出比单独化疗更多的益处。我们测试了有效的血管内皮生长因子抑制剂阿西替尼和紫杉醇/卡铂的联合应用，以确定在阿西替尼停药期间肿瘤增殖增强是否会导致持续的化疗敏感性。我们在转移性黑色素瘤患者中进行了一项前瞻性的II期试验，患者的ECOG表现状态为0-1，器官功能正常。阿西替尼5 mg PO b.i.d.卡铂(AuC=5)和紫杉醇(175 mg m−2)在第1天开始接受治疗。5例患者在第1、14、17、20天进行18F-脱氧-3‘-18F-氟胸苷(18F-Flt)-正电子发射计算机断层扫描，以评估肿瘤的增殖情况。治疗耐受性良好。最常见的3级不良反应是高血压、中性粒细胞减少症和贫血。未观察到4级非血液性不良反应。在完成18F-Flt-PET扫描的5名患者中，有4名患者在服用阿昔替尼期间SUV值增加(23-92%)。在36例可评价的患者中，有8例符合实体瘤疗效评价标准。总体而言，20名患者有SD，8名患者有PD作为最佳反应。中位PFS为8.7个月，中位总生存期为14.0个月。5例BRAFV600E/K患者的PFS明显比无这些突变的患者严重。阿昔替尼、卡铂和紫杉醇对BRAF野生型转移性黑色素瘤的耐受性和有效性良好。3‘-脱氧-3’-18F-氟代胸苷-正电子发射计算机断层扫描显示阿昔替尼停药后细胞增殖增加。
Simultaneous chemotherapy with vascular endothelial growth factor (VEGF) inhibition has not shown additional benefit over chemotherapy alone in advanced melanoma. We tested administration of the potent VEGF inhibitor axitinib followed by paclitaxel/carboplatin to determine whether enhanced tumour proliferation during axitinib withdrawal leads to sustained chemosensitivity. We conducted a prospective phase II trial in metastatic melanoma patients with ECOG performance status 0–1 and normal organ function. Axitinib 5 mg PO b.i.d. was taken on days 1–14 of each 21-day treatment cycle, and carboplatin (AUC=5) with paclitaxel (175 mg m−2) was administered on day 1 starting with cycle 2. 3′-Deoxy-3′-18F-fluorothymidine (18F-FLT)-PET scans were performed in five patients to assess tumour proliferation on days 1, 14, 17, and 20 of cycle 1. Molecular profiling for BRAF was performed for all patients with cutaneous, acral, or mucosal melanoma. The treatment was well tolerated. The most common grade 3 AEs were hypertension, neutropenia, and anaemia. Grade 4 non-haematologic AEs were not observed. Four of five patients completing 18F-FLT-PET scans showed increases (23–92%) in SUV values during the axitinib holiday. Of 36 evaluable patients, there were 8 confirmed PRs by Response Evaluation Criteria in Solid Tumors. Overall, 20 patients had SD and 8 had PD as the best response. The median PFS was 8.7 months and the median overall survival was 14.0 months. Five BRAFV600E/K patients had significantly worse PFS than patients without these mutations. Axitinib followed by carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type metastatic melanoma. 3′-Deoxy-3′-18F-fluorothymidine-PET scans showed increased proliferation during axitinib withdrawal.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
6.2
作者：
Kottschade, Lisa A.;Suman, Vera J.;Amatruda, Thomas, III;McWilliams, Robert R.;Mattar, Bassam I.;Nikcevich, Daniel A.;Behrens, Robert;Fitch, Tom R.;Jaslowski, Anthony J.;Markovic, Svetomir N.
通讯作者：
Markovic, Svetomir N.
影响因子：
158.5
作者：
Sandler, Alan;Gray, Robert;Johnson, David H.
通讯作者：
Johnson, David H.
血管内皮生长因子在转移性黑色素瘤中的表达增强。
影响因子：
8.8
作者：
Salven P;Heikkilä P;Joensuu H
通讯作者：
Joensuu H