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普萘洛尔介导的β阻断作用对皮肤血管肉瘤生长的抑制作用。

Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade.

机构信息

Mohs Micrographic Surgery and Cutaneous Oncology, San Leandro, California.

Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso.

出版信息

JAMA Dermatol. 2015 Nov;151(11):1226-9. doi: 10.1001/jamadermatol.2015.2554.

Abstract

IMPORTANCE

Patients with stage T2 multilesion angiosarcomas of the scalp and face that are larger than 10 cm demonstrate a 2-year survival rate of 0%. To our knowledge, major therapeutic advances against this disease have not been reported for decades. Preclinical data indicate that blocking β-adrenergic signaling with propranolol hydrochloride disrupts angiosarcoma cell survival and xenograft angiosarcoma progression.

OBSERVATIONS

A patient presented with a β-adrenergic-positive multifocal stage T2 cutaneous angiosarcoma (≥20 cm) involving 80% of the scalp, left forehead, and left cheek, with no evidence of metastasis. The patient was immediately administered propranolol hydrochloride, 40 mg twice a day, as his workup progressed and treatment options were elucidated. Evaluation of the proliferative index of the tumor before and after only 1 week of propranolol monotherapy revealed a reduction in the proliferative index of the tumor by approximately 34%. A combination of propranolol hydrochloride, 40 mg 3 times a day, paclitaxel poliglumex, 2 mg/m2 infused weekly, and radiotherapy during the subsequent 8 months resulted in extensive tumor regression with no detectable metastases.

CONCLUSIONS AND RELEVANCE

Our data suggest that β-blockade alone substantially reduced angiosarcoma proliferation and, in combination with standard therapy, is effective for reducing the size of the tumor and preventing metastases. If successful, β-blockade could be the first major advancement in the treatment of angiosarcoma in decades.

摘要

重要性

患有 T2 多病灶、头皮和面部、大于 10cm 的多发性血管肉瘤的患者,其 2 年生存率为 0%。据我们所知,针对这种疾病,几十年来尚未报道过重大的治疗进展。临床前数据表明,用盐酸普萘洛尔阻断β肾上腺素能信号可破坏血管肉瘤细胞的存活和异种移植物血管肉瘤的进展。

观察结果

一名患者患有β肾上腺素阳性、多灶性 T2 皮肤血管肉瘤(≥20cm),累及头皮的 80%、左前额和左脸颊,无转移证据。在进行检查和阐明治疗方案的同时,患者立即开始服用盐酸普萘洛尔,每天两次,每次 40mg。在单独使用普萘洛尔治疗仅 1 周后,评估肿瘤的增殖指数,发现肿瘤的增殖指数降低了约 34%。在随后的 8 个月中,将盐酸普萘洛尔(每天 40mg,每日 3 次)、紫杉醇聚谷氨酸(每周 2mg/m2 输注)和放疗联合应用,结果肿瘤广泛消退,无转移。

结论和相关性

我们的数据表明,β受体阻滞剂单独使用可显著降低血管肉瘤的增殖,并且与标准治疗联合使用可有效缩小肿瘤大小并预防转移。如果成功,β受体阻滞剂可能是血管肉瘤治疗几十年来的首次重大进展。

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