Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA.
J Clin Oncol. 2012 May 1;30(13):1476-83. doi: 10.1200/JCO.2011.39.6853. Epub 2012 Mar 19.
Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti-VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS.
Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately.
Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T(1)), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2).
Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients.
对于患有 HIV 相关性卡波西肉瘤（KS）的患者，理想的治疗方法是避免使用细胞毒性药物。血管内皮生长因子-A（VEGF-A）促进了 KS 的发病机制。我们评估了人源化抗 VEGF-A 单克隆抗体贝伐单抗在 HIV-KS 患者中的疗效。
接受高效抗逆转录病毒治疗（HAART）至少 1 个月后病情进展或 HAART 至少 4 个月后未消退的 HIV-KS 患者，给予贝伐单抗 15mg/kg，静脉注射，第 1 天和第 8 天各一次，然后每 3 周一次。主要观察终点为根据改良 AIDS 临床试验组（ACTG）的 HIV-KS 标准评估抗肿瘤活性。HIV 未感染者也符合入选条件并单独观察。
共纳入 17 例 HIV 感染者。14 例患者已经接受有效 HAART 治疗至少 6 个月（中位数为 1 年）。13 例患者为晚期疾病（ACTG T1），13 例患者曾接受过针对 KS 的化疗，7 例患者 CD4 计数<200 个/μL。中位治疗周期数为 10 个（范围为 1 至 37 个周期）；中位随访时间为 8.3 个月（范围为 3 至 36 个月）。16 例可评价患者的最佳肿瘤反应为完全缓解（CR）3 例（19%），部分缓解（PR）2 例（12%），稳定疾病 9 例（56%），进展疾病 2 例（12%）。总缓解率（CR+PR）为 31%（95%CI，11%至 58.7%）。5 例缓解者中有 4 例曾接受过针对 KS 的化疗。在 202 个周期的治疗中，至少可能与治疗相关的 3 至 4 级不良事件包括高血压（n=7）、中性粒细胞减少症（n=5）、蜂窝织炎（n=3）和头痛（n=2）。
贝伐单抗在 HIV-KS 患者中耐受良好，并在一部分患者中具有抗肿瘤活性。
