A pilot study with vincristine sulfate liposome infusion in patients with metastatic melanoma
A pilot study with vincristine sulfate liposome infusion in patients with metastatic melanoma
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DOI：
10.1097/cmr.0b013e328311aaa1
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发表时间：
2008-12-01
影响因子：
2.2
通讯作者：
Deitcher, Steven R.
中科院分区：
文献类型：
--
作者：
Bedikian, Agop Y.;Papadopoulos, Nicholas E.;Deitcher, Steven R.
硫酸长春新碱脂质体输注液（VSLI）是一种鞘磷脂/胆固醇脂质体包封长春新碱的制剂，可延长药物循环时间，并可能增强恶性肿瘤靶向、暴露和抗癌活性。我们评估了VSLI在转移性黑色素瘤患者中的安全性和活性。VSLI，提供VCR 2.0 mg/m2，无剂量上限，每2周一次输注1小时（1个周期）。确定了安全性、肿瘤缓解和存活率。治疗了27例原发性皮肤（n = 19）、葡萄膜（n = 4）、粘膜（n = 1）和未知（n=3）转移性黑色素瘤患者。25例（93%）患者既往接受过一种或多种化疗和/或免疫治疗; 14例（48%）接受过含长春碱的治疗方案。血液学不良事件（AE）主要表现为1/2级中性粒细胞减少。非血液学AE主要包括严重程度为1/2级的胃肠道和全身症状。3级AE包括1例感觉异常和4例便秘。26例可评价患者的疾病控制率为31%。发现1例完全缓解（葡萄膜黑色素瘤转移至肺）和2例部分缓解（先前未经治疗的皮肤黑色素瘤转移至骨、脑、脾和肺，另1例原发性未知的黑色素瘤累及肺、肝和淋巴结）。中位进展时间为1.9个月。中位生存期为9.6个月，30%的患者在1年时存活。VSLI通常耐受性良好，尤其对转移性黑色素瘤和葡萄膜黑色素瘤显示出有前景的抗肿瘤活性。正在进行一项II期试验，以进一步阐明VSLI在转移性葡萄膜黑色素瘤中的疗效和安全性。黑色素瘤研究18：400-404（C）2008年沃尔特斯Kluwer健康垂直酒吧Lippincott威廉姆斯&威尔金斯。
Vincristine sulfate liposome infusion (VSLI) is a sphingomyelin/cholesterol liposome encapsulated formulation of vincristine that results in an extended drug circulation time and the potential for enhanced malignancy targeting, exposure, and anticancer activity. We assessed the safety and activity of VSLI in patients with metastatic melanoma. VSLI, to provide VCR 2.0 mg/m(2) without dose capping, was infused over 1 h every 2 weeks (one cycle). Safety, tumor response, and survival were determined. Twenty-seven patients with metastatic melanoma of cutaneous (n = 19), uveal (n = 4), mucosal (n = 1), and unknown (n=3) primary were treated. Twenty-five (93%) patients had received one or more prior lines of chemotherapy and/or immunotherapy; 14 (48%) had received a vinblastine-containing regimen. Hematologic adverse events (AEs) primarily manifested as grade 1/2 neutropenia. Nonhematologic AEs primarily consisted of gastrointestinal and constitutional symptoms of grade 1/2 severity. Grade 3 AEs included one case of paresthesia and four cases of constipation. The disease control rate in 26 evaluable patients was 31%. One complete (uveal melanoma metastatic to lung) and two partial responses (previously untreated cutaneous melanoma metastatic to the bone, brain, spleen and lung, and another with melanoma of unknown primary involving the lung, liver, and lymph node) were found. Five patients had stable disease. The median time to progression was 1.9 months. The median survival was 9.6 months with 30% of the patients alive at 1 year. VSLI was generally well tolerated and showed promising antitumor activity against metastatic melanoma and uveal melanoma in particular. A phase 2 trial to further elucidate the efficacy and safety of VSLI in metastatic uveal melanoma is ongoing. Melanoma Res 18:400-404 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.