Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma.
Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma.
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DOI：
10.1002/ijc.25843
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发表时间：
2011-10-15
影响因子：
6.4
通讯作者：
Chiappori, Alberto
中科院分区：
文献类型：
--
作者：
Mahmood, S. Tariq;Agresta, Samuel;Vigil, Carlos E.;Zhao, Xiuhua;Han, Gang;D'Amato, Gina;Calitri, Ciara E.;Dean, Michelle;Garrett, Christopher;Schell, Michael J.;Antonia, Scott;Chiappori, Alberto
关键词：
软组织肉瘤（STS）代表了一组具有靶向分子改变的不同组织学亚型，通常作为单一疾病治疗。苹果酸舒尼替尼是一种多靶向受体酪氨酸激酶抑制剂，在携带类似改变的其他实体瘤中有活性（即，甲磺酸伊马替尼难治性胃肠道间质瘤）。这项单机构II期研究调查了苹果酸舒尼替尼在三种常见STS亚型中的安全性和有效性。有记录的不可切除或转移性STS（脂肪肉瘤、平滑肌肉瘤和恶性纤维组织细胞瘤[MFH]）、可测量的疾病和既往接受过3线或更少治疗的患者合格。治疗包括苹果酸舒尼替尼，每日50 mg，每6周一次，持续4周。入组了48例患者，35%的患者接受了大量预治疗（既往≥2线化疗）。其安全性特征与之前已知的苹果酸舒尼替尼毒性相似。脂肪肉瘤、平滑肌肉瘤和MFH的中位无进展生存期和总生存期分别为3.9和18.6个月、4.2和10.1个月、2.5和13.6个月。未经治疗和预治疗（化疗）的脂肪肉瘤、平滑肌肉瘤和MFH患者的3个月无进展率分别为75%和69.2%、60%和62.5%、25%和44.4%。需要注意的是，少数潜在惰性或低级别疾病的患者可能已被纳入，并且人数较少，3个月无进展率>40%表明苹果酸舒尼替尼至少在脂肪肉瘤和平滑肌瘤中具有活性。因此，我们认为，在这些敏感的STS亚型的进一步调查是必要的。
Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate-refractory gastrointestinal stromal tumors). This single-institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty-eight patients were enrolled, and 35% were heavily pretreated (≥2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression-free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1, and 2.5 and 13.6 months, respectively. The 3-month progression-free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma, and MFH were 75% and 69.2%, 60%, and 62.5%, and and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low-grade disease could have been included and the small numbers, a 3-month progression-free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted.
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影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
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作者：
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