Vascular targeting by EndoTAG™-1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer

被引：76

作者：

Eichhorn, Martin E. ^{[1
,2
]}

Ischenko, Ivan ^{[1
]}

Luedemann, Siiri ^{[2
]}

Strieth, Sebastian ^{[2
,3
]}

Papyan, Armine ^{[1
]}

Werner, Alexander ^{[4
]}

Bohnenkamp, Hermann ^{[5
]}

Guenzi, Eric ^{[5
]}

Preissler, Gerhard ^{[1
]}

Michaelis, Uwe ^{[5
]}

Jauch, Karl-Walter ^{[1
]}

Bruns, Christiane J. ^{[1
]}

Dellian, Marc ^{[3
]}

机构：

[1] Univ Munich, Klinikum Grosshadern, Dept Surg, D-81377 Munich, Germany

[2] Univ Munich, Walter Brendel Ctr Expt Med, D-81377 Munich, Germany

[3] Univ Munich, Klinikum Grosshadern, Dept Otorhinolaryngol, D-81377 Munich, Germany

[4] Bioserv Sci Labs GmbH, Planegg Martinsried, Germany

[5] Medigene AG, Planegg Martinsried, Germany

来源：

INTERNATIONAL JOURNAL OF CANCER | 2010年 / 126卷 / 05期

关键词：

tumor angiogenesis; vascular targeting therapy; cationic liposomes; paclitaxel; combination therapy; IMPROVES ANTITUMORAL EFFICACY; CATIONIC LIPOSOMES; ENDOTHELIAL-CELLS; PACLITAXEL; TUMORS; COMBINATION; ANGIOGENESIS; CHARGE;

D O I：

10.1002/ijc.24846

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Cationic lipid complexed paclitaxel (EndoTAG (TM)-1) is a novel vascular targeting agent for the treatment of cancer. Here, the aim was to investigate intratumoral drug distribution after EndoTAG (TM)-1 therapy and analyze the impact of EndoTAG (TM)-1 scheduling on antitumoral efficacy. The therapeutic effect of EndoTAG (TM)-1 in combination with conventional gemcitabine or cisplatin therapy was evaluated in L3.6pl orthotopic pancreatic cancer and a subcutaneous Lewis lung (LLC-1) carcinoma model. Oregon Green paclitaxel encapsulated in cationic liposomes in combination with intravital fluorescence microscopy clearly exhibited delivery of the drug by EndoTAG (TM)-1 to the tumor endothelium, whereas Oregon Green paclitaxel. dissolved in cremophor displayed an interstitial distribution pattern. The therapeutic efficacy of EndoTAG (TM)-1 was critically dependent on the application schedule with best therapeutic results using a metronomic rather than a maximum tolerated dose application sequence. The combination of EndoTAG (TM)-1 therapy and cytotoxic chemotherapy significantly enhanced antitumoral efficacy in both tumor models. Interestingly, only EndoTAG (TM)-1 in combination with gemcitabine was able to inhibit the incidence of metastasis in pancreatic cancer. In conclusion, vascular targeting tumor therapy by EndoTAG (TM)-1 combined with standard small molecular chemotherapy results in markedly enhanced antitumoral efficacy. Therefore, this combination represents a promising novel strategy for clinical cancer therapy.

引用

页码：1235 / 1245

页数：11

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