Any progress in the management of advanced pancreatic cancer? Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.
Any progress in the management of advanced pancreatic cancer? Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.
复制标题
晚期胰腺癌的治疗有何进展？
作者：
Jia Li;M. Saif
大多数胰腺癌患者都患有致命且难以治疗的晚期疾病。尽管常规使用化疗和放疗，但生存率并未显着提高；这种情况表明迫切需要新的治疗方法。用吉西他滨治疗晚期疾病对生存的影响不大，但对生活质量有良好的影响。迄今为止，目前与吉西他滨联合使用的靶向药物未能改善临床结果。这种失败可能源于胰腺癌的异质性分子发病机制，其中涉及多种致癌途径和明确的基因突变。然而，最近的数据支持这样的证据，即吉西他滨与厄洛替尼、卡培他滨或铂化合物的组合在晚期胰腺癌中可能比单独使用吉西他滨更有效。新的治疗策略，特别是使用分子靶向药物，正在评估中。已经确定了许多负责胰腺癌转化和进展的分子机制，这为确定可能的药理学靶点提供了可能性。胰腺癌仍然是美国癌症死亡的第四大原因。如何治疗不可切除的胰腺癌一直是所有医学肿瘤学家面临的一个具有挑战性的话题。自 1997 年以来，历史上的 5-氟尿嘧啶已被单药吉西他滨取代。以吉西他滨为骨干的多种组合已在临床试验中进行了测试；不幸的是，没有一种组合（包括与生物制剂的组合）被证明明显优于单独使用吉西他滨。今年，我们对更多的组合进行了研究，并在会议上公布了结果。在一线环境中，两项大型 III 期试验（摘要#4504 和#4601）未能证明第二种细胞毒性药物或疫苗有任何额外益处。吉西他滨治疗失败后，可考虑将亚叶酸加 5-FU 加奥沙利铂 (FOLFOX) 和 5-氟尿嘧啶加亚叶酸加伊立替康 (FOLFIRI) 作为二线治疗（摘要 #4618）。新型代理（摘要#4501、#4625、#4626、#4617）带来了一些希望；然而，总的来说，所有组合仍然严重依赖吉西他滨的支柱。现在，超越吉西他滨的框框思考并探索新型药物非常重要。
Majority of the patients with pancreatic cancer present with advanced disease that is lethal and notoriously difficult to treat. Survival has not improved dramatically despite routine use of chemotherapy and radiotherapy; this situation signifies an urgent need for novel therapeutic approaches. The treatment of advanced disease with gemcitabine has only a modest activity on survival with a favorable impact on quality of life. So far, the current targeted agents that have been used in combination with gemcitabine have failed to improve clinical outcomes. This failure may stem from the heterogeneous molecular pathogenesis of pancreatic cancers, which involves several oncogenic pathways and defined genetic mutations. However, recent data support the evidence that the combination of gemcitabine with erlotinib, capecitabine or platinum compounds could be more active than gemcitabine alone in advanced pancreatic cancer. New therapeutic strategies, particularly using molecular target agents, are under evaluation. A number of molecular mechanisms responsible of transformation and progression of pancreatic cancer have been identified, opening the possibility to identify also possible pharmacological targets. Pancreatic cancer remains the 4th leading cause of cancer death in the U.S.A.. How to treat a non-resectable pancreatic cancer has been a challenging topic for all medical oncologists. Historical 5-fluorouracil has been replaced by single agent gemcitabine since 1997. Numerous combinations using gemcitabine as a backbone have been tested in clinical trials; unfortunately, none of the combinations including the ones with biological agents was proved to be significantly superior to gemcitabine alone. This year, more combinations were investigated and the results were presented on the meeting. In first-line setting, two large phase III trials (Abstracts #4504 and #4601) failed to prove any additional benefit of a second cytotoxic agent or a vaccine. Folinic acid plus 5-FU plus oxaliplatin (FOLFOX) and 5-fluorouracil plus leucovorin plus irinotecan (FOLFIRI) could be considered in the second-line setting after failure of gemcitabine therapy (Abstract #4618). Novel agents (Abstracts #4501, #4625, #4626, #4617) provide some hope; however, in general, all combinations are still significantly relying on the backbone of gemcitabine. Thinking beyond the gemcitabine box and exploring novel agents are very crucial now.