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Vascular targeting by EndoTAG™‐1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer
Author(s) -
Eichhorn Martin E.,
Ischenko Ivan,
Luedemann Siiri,
Strieth Sebastian,
Papyan Armine,
Werner Alexander,
Bohnenkamp Hermann,
Guenzi Eric,
Preissler Gerhard,
Michaelis Uwe,
Jauch KarlWalter,
Bruns Christiane J.,
Dellian Marc
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24846
Subject(s) - gemcitabine , pancreatic cancer , medicine , chemotherapy , paclitaxel , combination therapy , lung cancer , metastasis , cancer , distribution (mathematics) , pharmacology , oncology , cancer research , mathematical analysis , mathematics
Cationic lipid complexed paclitaxel (EndoTAG™‐1) is a novel vascular targeting agent for the treatment of cancer. Here, the aim was to investigate intratumoral drug distribution after EndoTAG™‐1 therapy and analyze the impact of EndoTAG™‐1 scheduling on antitumoral efficacy. The therapeutic effect of EndoTAG™‐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™‐1 to the tumor endothelium, whereas Oregon Green paclitaxel dissolved in cremophor displayed an interstitial distribution pattern. The therapeutic efficacy of EndoTAG™‐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™‐1 therapy and cytotoxic chemotherapy significantly enhanced antitumoral efficacy in both tumor models. Interestingly, only EndoTAG™‐1 in combination with gemcitabine was able to inhibit the incidence of metastasis in pancreatic cancer. In conclusion, vascular targeting tumor therapy by EndoTAG™‐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.