New therapeutic directions for advanced pancreatic cancer: Targeting the epidermal growth factor and vascular endothelial growth factor pathways
New therapeutic directions for advanced pancreatic cancer: Targeting the epidermal growth factor and vascular endothelial growth factor pathways
复制标题
DOI：
10.1634/theoncologist.2007-0134
复制
发表时间：
2008-01-01
期刊：
影响因子：
5.8
通讯作者：
Rocha-Lima, Caio
中科院分区：
文献类型：
--
作者：
Burris, Howard, III;Rocha-Lima, Caio
在晚期胰腺癌中，单药吉西他滨大约在10年前成为标准治疗。随后，吉西他滨与氟尿嘧啶、顺铂、伊立替康、奥沙利铂或培美曲塞联合使用没有明显的生存获益。在较新的方法中，靶向人表皮生长因子受体（HER- 1/ EGFR）显示出前景。美国食品和药物管理局最近批准厄洛替尼（HER- 1/ EGFR酪氨酸激酶抑制剂）联合吉西他滨用于晚期胰腺癌的一线治疗。在局部晚期或转移性疾病中，该联合治疗比单独使用吉西他滨具有统计学意义的生存获益（中位总生存时间为6.24个月对5.91个月；风险比为0.82;p = 0.038）；然而，这种生存差异的临床意义一直受到质疑。此外，据报道，在一项大型III期试验中，在吉西他滨中添加西妥昔单抗（一种抗HER- 1/ EGFR单克隆抗体[mAb]）未能导致比单独使用吉西他滨更长的总生存时间。贝伐单抗（一种重组的人源化IgG(1)单抗，与VEGF结合）联合吉西他滨靶向血管内皮生长因子（VEGF）在一项II期试验中进行了研究，取得了令人鼓舞的结果，不幸的是，随后的III期研究没有得到支持。虽然未来胰腺癌的治疗可能会受到某些生物标志物的潜在影响，以预测对分子靶向治疗的更好反应，从而允许患者治疗的个体化，但目前还没有明确的候选药物，这仍然是一个值得进一步研究的有趣领域。
In advanced pancreatic cancer, single- agent gemcitabine became the standard therapy approximately 10 years ago. Subsequently, combinations of gemcitabine with fluorouracil, cisplatin, irinotecan, oxaliplatin, or pemetrexed produced no clear survival benefit. Among the newer approaches, targeting human epidermal growth factor receptor ( HER- 1/ EGFR) shows promise. The U. S. Food and Drug Administration recently approved erlotinib ( a HER- 1/ EGFR tyrosine kinase inhibitor) combined with gemcitabine for the first- line treatment of advanced pancreatic cancer. This combination showed a statistically significant survival benefit over gemcitabine alone in locally advanced or metastatic disease ( the median overall survival time was 6.24 months versus 5.91 months; hazard ratio, 0.82; p =.038); however, the clinical significance of this survival difference has been questioned. Additionally, a large phase III trial where the addition of cetuximab ( an anti - HER- 1/ EGFR monoclonal antibody [ mAb]) to gemcitabine failed to result in a longer overall survival time than with gemcitabine alone has been reported. Targeting vascular endothelial growth factor ( VEGF) with bevacizumab ( a recombinant, humanized IgG(1) mAb that binds to VEGF) in combination with gemcitabine was investigated in a phase II trial, with promising outcomes that were unfortunately not supported by a subsequent phase III study. While the future treatment of pancreatic cancer may be influenced by the potential of certain biomarkers to predict better response to molecular- targeted therapies, allowing individualization of patient therapy, there are currently no clear candidates, and this remains an interesting area for further investigation.