Seiwert Tanguy Y, Cohen Ezra E W
Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL 60637-1470, USA.
Semin Oncol. 2008 Jun;35(3):274-85. doi: 10.1053/j.seminoncol.2008.03.005.
Tumor angiogenesis is a hallmark of advanced cancers and an attractive treatment target in multiple solid tumors. In the past 5 years anti-angiogenic therapies have seen a rapid ascent into mainstream clinical practice. For head and neck cancer (HNC), definitive evidence in the form of a pivotal trial is still pending. Nevertheless, preclinical and early clinical data support a central role of angiogenesis for HNC: up to 90% of HNCs express angiogenic factors such as vascular endothelial growth factor (VEGF) and the respective receptors (VEGFR1-3), and multiple studies support the prognostic implications of angiogenic markers for this tumor. Contrary to concerns that anti-angiogenic therapies could increase hypoxia and thereby treatment resistance, anti-angiogenic therapies in preclinical models appear to overcome resistance and preclinically synergize with traditional therapies, eg, radiation. Clinical use of anti-angiogenic agents for HNC, including bevacizumab, sorafenib, sunitinib, and others, is currently limited to clinical trials, and several larger trials are still ongoing. Single-agent anti-angiogenic drugs so far have not shown activity in unselected HNC patients, with a response rate of less than 4% for the small molecule anti-angiogenics sorafenib and the investigational agent SU5416. On the other hand, combinations of anti-angiogenic drugs with other treatments (analogous to other solid tumors) appear promising; for example, the combination of bevacizumab with the EGFR inhibitor erlotinib showed a response rate of 14.6%. Studies of bevacizumab with chemotherapy (phase III Eastern Cooperative Oncology Group [ECOG] trial) and in combination with chemoradiation are currently ongoing. The side effect profile is comparable to what has been observed in other tumor types and include hypertension, proteinuria, and thrombotic and hemorrhagic events. With the intense research effort preclinically and clinically, and some encouraging early results, anti-angiogenic therapies and biomarkers appear to be poised to play an important role in the treatment of HNC in the near future.
肿瘤血管生成是晚期癌症的一个标志，也是多种实体瘤中一个有吸引力的治疗靶点。在过去5年里，抗血管生成疗法迅速进入主流临床实践。对于头颈癌（HNC），以关键试验形式存在的确凿证据仍有待确定。然而，临床前和早期临床数据支持血管生成在头颈癌中起核心作用：高达90%的头颈癌表达血管生成因子，如血管内皮生长因子（VEGF）及其相应受体（VEGFR1 - 3），多项研究支持血管生成标志物对该肿瘤的预后影响。与抗血管生成疗法可能增加缺氧从而导致治疗抵抗的担忧相反，临床前模型中的抗血管生成疗法似乎能克服抵抗，并在临床前与传统疗法（如放疗）协同作用。抗血管生成药物用于头颈癌的临床应用，包括贝伐单抗、索拉非尼、舒尼替尼等，目前仅限于临床试验，仍有几项大型试验正在进行。到目前为止，单药抗血管生成药物在未选择的头颈癌患者中尚未显示出活性，小分子抗血管生成药物索拉非尼和研究药物SU5416的缓解率低于4%。另一方面，抗血管生成药物与其他治疗方法联合使用（类似于其他实体瘤）似乎很有前景；例如，贝伐单抗与表皮生长因子受体（EGFR）抑制剂厄洛替尼联合使用时缓解率为14.6%。目前正在进行贝伐单抗与化疗联合（东部肿瘤协作组[ECOG]III期试验）以及与放化疗联合使用的研究。其副作用谱与在其他肿瘤类型中观察到的情况相当，包括高血压、蛋白尿以及血栓形成和出血事件。随着临床前及临床研究的大力开展，以及一些令人鼓舞的早期结果，抗血管生成疗法和生物标志物似乎在不久的将来有望在头颈癌治疗中发挥重要作用。
