Medical treatment of advanced colorectal cancer in 2009.
Medical treatment of advanced colorectal cancer in 2009.
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DOI：
10.1177/1758834009343302
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发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Grothey, Axel
中科院分区：
文献类型：
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作者：
Grothey, Axel
晚期结直肠癌（CRC）的药物治疗目前可用的治疗方案似乎是丰富的财富。奥沙利铂和伊立替康作为常规细胞毒性药物以及贝伐珠单抗和表皮生长因子受体（EGFR）抗体、西妥昔单抗和帕尼单抗作为新型靶向药物整合到标准药物治疗中，使转移性CRC的中位总生存期延长至2年以上。CRC患者结局的这些显著改善与可用于治疗这种疾病的活性药物的数量密切相关，这一点怎么强调都不过分。然而，治疗选择的丰富性带来了晚期CRC姑息性药物治疗的实际管理的具体挑战，特别是关于靶向药物的利用。在这种情况下，贝伐珠单抗已成为一线化疗的标准组成部分。迄今为止，尚未鉴定出贝伐珠单抗在转移性CRC中的活性的预测标志物，这对于临床实践是有意义的。在姑息治疗环境中使用贝伐珠单抗的关键问题是，在肿瘤进展后继续使用贝伐珠单抗是否能提供临床获益，以及哪些患者组发生贝伐珠单抗相关毒性的风险更高。西妥昔单抗和帕尼单抗已经证明了与化疗联合或与贝伐单抗相比作为单药的疗效。在NSCLC患者中，两种EGFR抗体对时间相关参数、无进展生存期和总生存期的影响最多是中等的，更多地强调在选定的患者组中诱导肿瘤应答。因此，直到最近，EGFR抗体主要被视为挽救治疗选择，特别是因为在后续治疗中使用时似乎没有失去活性。携带KRAS（和BRAF）突变的CRC对EGFR抗体具有耐药性，这一发现使我们能够丰富有机会从西妥昔单抗或帕尼单抗治疗中获益的CRC患者人群。因此，基于生物标志物的治疗决策现在是CRC临床实践和试验设计的一个组成部分。总之，靶向药物已成为晚期CRC药物治疗的一个组成部分。目前肿瘤学实践的挑战是开发一种合理的基于生物标志物的治疗算法，利用所有潜在的活性药物作为个体化治疗。
The treatment options currently available in the medical therapy of advanced colorectal cancer (CRC) appear to be an abundance of riches. The integration of oxaliplatin and irinotecan as conventional cytotoxic agents as well as bevacizumab and the epidermal growth factor receptor (EGFR) antibodies, cetuximab and panitumumab, as novel targeted agents into standard medical therapy have improved median overall survival in metastatic CRC beyond 2 years. It cannot be overemphasized that these significant improvements in outcome of patients with CRC are closely linked to the number of active drugs available to treat this disease. The abundance of treatment options, however, comes with specific challenges for the practical management of palliative medical therapy in advanced CRC, in particular with regard to the utilization of targeted agents. In this context, bevacizumab has established itself as the standard component of first-line chemotherapy. It is of interest for clinical practice that so far no predictive marker for the activity of bevacizumab in metastatic CRC has been identified. The key questions surrounding the use of bevacizumab in the palliative setting are whether its continuation beyond tumor progression provides clinical benefit, and which patient group is at higher risk for bevacizumab-related toxicities. Cetuximab and panitumumab have demonstrated efficacy both in combination with chemotherapy or - in contrast to bevacizumab - as single agent. In unselected patients, the effect of both EGFR antibodies on time-related parameters, progression free survival and overall survival, is moderate at best with emphasis more on the induction of tumor responses in a select group of patients. Therefore, until recently, EGFR antibodies were mainly regarded as salvage therapy options, in particular, since there did not appear to be a loss of activity when used in later lines of therapy. The finding that CRC harboring KRAS (and BRAF) mutations are resistant to EGFR antibodies, has allowed us to enrich the patient population with CRC that have a chance to benefit from cetuximab or panitumumab therapy. Biomarker-based treatment decisions are therefore now an integral part of clinical practice and trial design in CRC. In conclusion, targeted agents have become an integral part of medical therapy for advanced CRC. The challenge for current oncologic practice is to develop a rationale and biomarker-based treatment algorithm utilizing all potentially active agents as individualized therapy.