Bristol-Myers Squibb Company, P.O. Box 4000, K22-03, Princeton, NJ 08543, USA.
Ther Adv Med Oncol. 2011 Jan;3(1):11-25. doi: 10.1177/1758834010386402.
Ixabepilone demonstrates marked synergistic activity in combination with capecitabine, which served as the rationale for the evaluation of this combination in the clinic. Ixabepilone plus capecitabine is currently approved for patients with locally advanced or metastatic breast cancer (MBC) progressing after treatment with an anthracycline and a taxane; approval was based on the results of two phase III trials comparing the combination with capecitabine monotherapy. An array of preclinical studies in multiple solid tumor types show that ixabepilone demonstrates therapeutic synergy with targeted therapies including trastuzumab, bevacizumab, brivanib, and cetuximab; with immune-modulating agents such as anti-CTLA-4 antibody; and with other chemotherapy drugs such as irinotecan and epirubicin. Notably, experiments in several xenograft models show that ixabepilone provides greater antitumor synergism when combined with bevacizumab than either paclitaxel or nab-paclitaxel combined with bevacizumab. These preclinical findings provide a foundation for ongoing phase II clinical trials using ixabepilone in combination with trastuzumab or lapatinib in HER2-positive breast cancer; with bevacizumab in breast cancer, endometrial cancer, renal cancer, and non-small cell lung cancer (NSCLC); with cetuximab in breast cancer, NSCLC, and pancreatic cancer; and with brivanib, dasatinib, sorafinib, sunitinib, or vorinostat in MBC. Preliminary results from several of these trials suggest that ixabepilone-based combinations have promising anticancer activity.
伊沙匹隆与卡培他滨联合具有显著的协同作用，这为该联合在临床中的评估提供了依据。伊沙匹隆加卡培他滨目前被批准用于接受蒽环类和紫杉烷治疗后进展的局部晚期或转移性乳腺癌（MBC）患者；批准的依据是两项比较联合卡培他滨单药治疗的 III 期临床试验结果。多项实体瘤类型的临床前研究表明，伊沙匹隆与曲妥珠单抗、贝伐珠单抗、brivanib 和西妥昔单抗等靶向治疗药物、抗 CTLA-4 抗体等免疫调节药物以及伊立替康和表柔比星等其他化疗药物具有治疗协同作用。值得注意的是，几项异种移植模型实验表明，与紫杉醇或nab-紫杉醇联合贝伐珠单抗相比，伊沙匹隆联合贝伐珠单抗具有更强的抗肿瘤协同作用。这些临床前发现为正在进行的 II 期临床试验提供了基础，这些临床试验将伊沙匹隆与曲妥珠单抗或拉帕替尼联合用于 HER2 阳性乳腺癌；与贝伐珠单抗联合用于乳腺癌、子宫内膜癌、肾癌和非小细胞肺癌（NSCLC）；与西妥昔单抗联合用于乳腺癌、NSCLC 和胰腺癌；与 brivanib、达沙替尼、索拉非尼、舒尼替尼或 vorinostat 联合用于 MBC。这些试验中的几项初步结果表明，基于伊沙匹隆的联合具有很有前途的抗癌活性。
