Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Cancer. 2013 Feb 1;119(3):586-92. doi: 10.1002/cncr.27760. Epub 2012 Aug 22.
Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM).
A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m(2) on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m(2) , or 80 mg/m(2) post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%.
Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%-51.2%) for TB and 56.1% (90% confidence interval: 44.7%-70.4%) for ABC.
The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues.
越来越多的证据表明，化疗联合血管内皮生长因子（VEGF）抑制是转移性黑色素瘤（MM）患者的一种临床有效治疗方法。
在未接受过化疗的不可切除的 IV 期 MM 患者中进行了一项 2 期试验，这些患者被随机分配至替莫唑胺（200mg/m2，第 1 至 5 天）和贝伐珠单抗（10mg/kg，静脉注射，第 1 天和第 15 天）每 28 天一次（TB 方案），或nab-紫杉醇（100mg/m2，或由于毒性增加至 80mg/m2，第 1、8 和 15 天）、贝伐珠单抗（10mg/kg，第 1 天和第 15 天）和卡铂（第 1 天 AUC6，或添加物后第 5 天 AUC5）每 28 天一次（ABC 方案）。每个方案的入组目标为 41 例患者。该研究的主要目的是估计每个方案的 6 个月无进展生存率（PFS6）。如果方案的 PFS6 率大于 60%，则认为该方案有前景。
93 例符合条件的患者（42 例 TB 和 51 例 ABC）被纳入研究。大多数患者患有 M1c 疾病（20 例 TB 和 26 例 ABC）。ABC 方案的中位 PFS 和总生存期分别为 6.7 个月和 13.9 个月。TB 方案的中位 PFS 时间和中位总生存期分别为 3.8 个月和 12.3 个月。两种方案中最常见的严重毒性（≥3 级）是细胞减少症、疲劳和血栓形成。在每个方案中入组的前 41 例患者中，TB 组的 PFS6 率为 32.8%（95%置信区间：21.1%-51.2%），ABC 组为 56.1%（90%置信区间：44.7%-70.4%）。
尽管存在耐受性问题，但贝伐珠单抗联合 nab-紫杉醇和卡铂的添加显示出有前景的活性。
