Gemzar verpakt en toegediend in speciaal geprepareerde vetbolletjes - cationic liposomen ( EndoTAG-1) verdubbelt bijna overlevingstijd (van 7,2 naar 13,6 maanden mediaan) van inoperabele alvleesklierkankerpatienten

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18 september 2008: Bron: Reuters

Een tussenrapport van een fase II studie toont aan dat wanneer Gemzar wordt gegeven verpakt in speciaal geprepareerde vetbolletjes , de zogeheten Endo Tag-1 methode , dan is de effectiviteit significant beter met darbij ook nog minder bijwerkingen dan wanneer Gemzar systemisch wordt toegediend.. Deze methode van chemo verpakken in liposomen wordt ook al toegepast bij o.a.paclitaxel verpakt in liposomen bij borstkanker. Medigene het bedrijf dat deze studie heeft opgezet is nu al naar butien gekomen , aldus Reuters , met deze uitkomsten omdat deze spectaculair goed te noemen zijn. Er zit wel verschil in de gebruiikte speciaal geprepareerde vetbolletjes waarin ik niet goed begrijp wat het verschil is maar in deze studie zijn cationic liposomen gebruikt. Maar vraag uw arts hiernaar. Onder artikel van Reuters heb ben we een studie geplaatst die beschrijft wat chemo (in dit voorbeeld cisplatin) toedienen met liposomen inhoudt

By Ben Hirschler

LONDON, Sept 16 (Reuters) - Patients with inoperable pancreatic cancer live substantially longer when given MediGene's (MDGGn.DE: Quote, Profile, Research) experimental drug EndoTAG-1 on top of standard chemotherapy, according to clinical trial results.

EndoTAG-1, the German biotech company's most important pipeline product, has already elicited interest from several large pharmaceutical companies keen to strike a partnership deal.

Results of a mid-stage Phase II trial presented on Tuesday showed patients given the new drug in combination with the older treatment gemcitabine survived up to 13.6 months compared with an average 7.2 months for those on gemcitabine alone.

"These results are the best I have ever seen in palliative treatment in pancreatic cancer," Matthias Loehr from Sweden's Karolinska Institute told the annual meeting of the European Society of Medical Oncology (ESMO) in Stockholm.

"The results are really excellent and a Phase III study is in the making," he added.

Phase III is the final stage of testing before a new drug is submitted to regulators for approval.

MediGene's drug -- a combination of fat molecules and another cancer drug called paclitaxel -- is designed to destroy new blood vessels that grow around tumours. It does this in a different way to products like Genentech (DNA.N: Quote, Profile, Research) and Roche's (ROG.VX: Quote, Profile, Research) Avastin.

EndoTAG-1 consists of charged particles that bind preferentially to blood vessel cells, after which paclitaxel is released and directly stops blood vessel growth. Paclitaxel, when given conventionally, is not very effective in pancreatic cancer.

Pancreatic cancer patients typically have a poor prognosis because the cancer usually causes no symptoms early on. As a result, it is often advanced by the time it is diagnosed.

MediGene believes EndoTAG-1 has the potential to achieve annual sales of more than 1 billion euros ($1.40 billion) a year, if it progresses successfully in clinical development for pancreatic and other types of cancer.

Results of a clinical trial testing the medicine in breast cancer are expected in 2009.

The companies involved declined to comment. (Editing by Sue Thomas)

1: Clin Cancer Res. 2008 Jul 15;14(14):4603-11. Links

Paclitaxel encapsulated in cationic liposomes increases tumor microvessel leakiness and improves therapeutic efficacy in combination with Cisplatin.

Strieth S, Eichhorn ME, Werner A, Sauer B, Teifel M, Michaelis U, Berghaus A, Dellian M.

Department of Otorhinolaryngology, Campus Grosshadern, University of Munich, Munich, Germany. sebastian.strieth@med.uni-muenchen.de

PURPOSE: Paclitaxel encapsulated in cationic liposomes (EndoTAG-1) is a vascular targeting formulation for the treatment of solid tumors. It triggers intratumoral microthrombosis, causing significant inhibition of tumor perfusion and tumor growth associated with endothelial cell apoptosis. Here, we quantified the effects of repeated EndoTAG-1 therapy on tumor microvascular leakiness with respect to leukocyte-endothelial cell interactions, the targeting property of cationic liposomes, and the therapeutic combination with conventional cisplatin chemotherapy.

EXPERIMENTAL DESIGN: Using dorsal skinfold chamber preparations in Syrian Golden hamsters, in vivo fluorescence microscopy experiments were done after repeated EndoTAG-1 treatment of A-Mel-3 tumors. Controls received glucose, paclitaxel alone, or cationic liposomes devoid of paclitaxel. Extravasation of rhodamine-labeled albumin was measured to calculate microvessel permeability, and intratumoral leukocyte-endothelial cell interactions were quantified. Subcutaneous tumor growth was evaluated after combination therapy followed by histologic analysis.

RESULTS: Microvascular permeability was significantly increased only after treatment with EndoTAG-1, whereas intratumoral leukocyte-endothelial cell interactions were not affected by any treatment. In separate skinfold chamber experiments, fluorescently labeled cationic liposomes kept their targeting property for tumor endothelial cells after repeated EndoTAG-1 treatment and no signs of extravasation were observed. Subcutaneous A-Mel-3 tumor growth was significantly inhibited by the combination of cisplatin and EndoTAG-1.

CONCLUSIONS: These data show that vascular targeting with EndoTAG-1 increases tumor microvessel leakiness probably due to vascular damage. This mechanism is not mediated by inflammatory leukocyte-endothelial cell interactions. Manipulating the blood-tumor barrier by repeated tumor microvessel targeting using EndoTAG-1 can effectively be combined with tumor cell-directed conventional cisplatin chemotherapy.

PMID: 18628475 [PubMed - indexed for MEDLINE]

vetbolletjes, liposomen, Gemzar, pancreaskanker, alvleesklierkanker