Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
J Clin Oncol. 2011 Mar 20;29(9):1140-5. doi: 10.1200/JCO.2010.33.3591. Epub 2011 Feb 22.
We hypothesized that bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), will potentiate the activity of pemetrexed, a multitargeted antifolate, in squamous cell carcinoma of the head and neck (SCCHN).
Patients with previously untreated, recurrent, or metastatic SCCHN were treated with pemetrexed 500 mg/m(2) and bevacizumab 15 mg/kg given intravenously every 21 days with folic acid and B(12) supplementation until disease progression. Primary end point was time-to-progression (TTP). DNA was isolated from whole blood samples for the detection of polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase (MTHFR), and VEGF.
Forty patients were enrolled. The median TTP was 5 months, and the median overall survival (OS) was 11.3 months. In 37 evaluable patients, the overall response rate was 30%, including a complete response rate of 5%, and the disease control rate was 86%. Grade 3 to 5 bleeding events occurred in six patients (15%): four were grade 3, and two were fatal. Other serious toxicities in 10% or more of patients included neutropenia (10%) and infection (12.5%). One patient died of sepsis after receiving eight cycles of therapy. For the MTHFR A1298C (rs1801131) single nucleotide polymorphisms, homozygote patients with AA had worse OS (P = .034).
The addition of bevacizumab to pemetrexed resulted in promising efficacy outcomes in SCCHN. Bleeding events were frequent but some may have been due to natural history of disease. Polymorphisms in MTHFR may offer potential for treatment individualization.
我们假设贝伐单抗，一种针对血管内皮生长因子（VEGF）的单克隆抗体，将增强培美曲塞的活性，培美曲塞是一种多靶点抗叶酸药物，用于头颈部鳞状细胞癌（SCCHN）。
未经治疗、复发或转移性 SCCHN 的患者接受培美曲塞 500mg/m² 和贝伐单抗 15mg/kg 静脉注射，每 21 天一次，并补充叶酸和 B12，直到疾病进展。主要终点是无进展生存期（TTP）。从全血样本中提取 DNA，用于检测胸苷酸合成酶、亚甲基四氢叶酸还原酶（MTHFR）和 VEGF 的多态性。
共纳入 40 例患者。中位 TTP 为 5 个月，中位总生存期（OS）为 11.3 个月。在 37 例可评估患者中，总缓解率为 30%，包括完全缓解率为 5%，疾病控制率为 86%。6 例患者（15%）发生 3 级至 5 级出血事件：4 例为 3 级，2 例为致命性。其他 10%或更多患者出现严重毒性，包括中性粒细胞减少症（10%）和感染（12.5%）。1 例患者在接受 8 个周期治疗后死于败血症。对于 MTHFR A1298C（rs1801131）单核苷酸多态性，AA 纯合子患者的 OS 更差（P=0.034）。
贝伐单抗联合培美曲塞治疗 SCCHN 取得了有前景的疗效。出血事件频繁，但部分可能与疾病自然史有关。MTHFR 多态性可能为个体化治疗提供潜力。
