Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
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DOI：
10.1371/journal.pone.0048787
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sondak VK
中科院分区：
文献类型：
--
作者：
Bhatia S;Moon J;Margolin KA;Weber JS;Lao CD;Othus M;Aparicio AM;Ribas A;Sondak VK
Sorafenib是一种细胞增殖和血管生成的多激酶抑制剂，可抑制在大多数葡萄膜黑色素瘤中激活的丝裂原激活的蛋白激酶途径。这项II期研究由SWOG合作小组进行，旨在评估索拉非尼联合卡铂和紫杉醇（CP）治疗转移性葡萄膜黑色素瘤的疗效。25例IV期葡萄膜黑色素瘤患者既往接受过0-1次全身治疗。治疗包括长达6个周期的卡铂（AUC = 6）和紫杉醇（225mg /m2），第1天静脉注射加索拉非尼（400mg PO，每日两次），随后索拉非尼单药治疗直到疾病进展。主要终点为客观缓解率（ORR）；采用两阶段设计，如果在前20名可评估的患者中未观察到确认的反应，则终止研究。次要疗效终点包括无进展生存期（PFS）和总生存期（OS）。在24例可评估的患者中，没有证实的客观反应（ORR = 0% [95% CI: 0-14%]），研究在第一阶段终止。24例患者中有11例（45%）出现轻微反应（肿瘤消退小于30%）。中位PFS为4个月[95% CI: 1-6个月]，6个月PFS为29% [95% CI: 13%-48%]。中位OS为11个月[95% CI: 7-14个月]。在这项研究中，尽管在一些患者中观察到轻微的肿瘤反应和稳定的疾病，但当用ORR评估CP +索拉非尼治疗转移性葡萄膜黑色素瘤的总体疗效时，不值得进一步的临床试验。ClinicalTrials.gov NCT00329641
Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma. Twenty-five patients with stage IV uveal melanoma who had received 0–1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m2) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0–14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1–6 months] and the 6-month PFS was 29% [95% CI: 13%–48%]. The median OS was 11 months [95% CI: 7–14 months]. In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients. ClinicalTrials.gov NCT00329641
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DOI：
10.1097/coc.0b013e3181d2ed67
发表时间：
2011-02
期刊：
American journal of clinical oncology
影响因子：
--
作者：
Guenterberg KD;Grignol VP;Relekar KV;Varker KA;Chen HX;Kendra KL;Olencki TE;Carson WE 3rd
通讯作者：
Carson WE 3rd
影响因子：
2
作者：
GREEN, SJ;DAHLBERG, S
通讯作者：
DAHLBERG, S
影响因子：
8.8
作者：
Neale, MH;Myatt, N;Cree, IA;Kurbacher, CM;Foss, AJE;Hungerford, JL;Plowman, PN
通讯作者：
Plowman, PN
影响因子：
2.3
作者：
Myatt, N;Cree, IA;Plowman, PN
通讯作者：
Plowman, PN
影响因子：
3.4
作者：
Kupsch, Petra;Henning, Bernhard F;Strumberg, Dirk
通讯作者：
Strumberg, Dirk