FP29-1 Investigation of novel chemotherapeutic combinations in a tumor model for adrenocortical carcinoma

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP29-Adrenal Tumors & Pheochromocytoma
Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:45 AM
Room 134 (Moscone Center)

Poster Board MON-3
Constanze Hantel*1, Sara Jung1, Thomas Mussack2, Martin Reincke3 and Felix Beuschlein3
1University of munich, Munich, Germany, 2University of munich, Munich, 3University of Munich, Munich, Germany
Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane (M). Recently, we investigated in combination with M the effects of two different chemotherapies on human NCIh295 cells in vitro: 1. The classical EDP (etoposide, doxorubicin, cisplatin) and 2. a novel paclitaxel containing scheme PDP (paclitaxel, doxorubicin, cisplatin) indicating anti-tumoral superiority of PDP-M over EDP-M regarding cell viability (p=0.001), apoptosis (p=0.001) and proliferation (p˂0.01). Since we found furthermore evidence for an extraordinary uptake phenomenon of liposomes by ACC cells we included for consecutive in vivo experiments liposomal variants of the treatment schemes called LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin) and LPDP-M (nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin). In short-term therapeutic experiments on NCIh295 tumor-bearing mice EDP-M did not induce a significant loss of tumor cells while the novel treatment schemes PDP-M (p˂0.01), LEDP-M (p˂0.01) and LPDP-M (p˂0.01) resulted overall in a significant reduction in the number of tumor cells compared with controls. LEDP-M (p˂0.01) and LPDP-M (p˂0.05) induced furthermore apoptosis as quantified by TUNEL staining. Similar effects were detectable with TUNEL on patient’s ACC-xenografts comparing LPDP-M with PDP-M (p˂0.05), but not between EDP-M and LEDP-M. Blood counts of PDP-M and LPDP-M treated mice showed a tendency to leukocyte reduction without statistical significance versus controls, while EDP-M and LEDP-M treatments lead to leucopenia (p<0.01). HE-stained kidneys from LEDP-M and LPDP-M treated mice appeared unaffected in comparison to controls, kidneys from EDP-M and PDP-M treatment groups showed by trend a reduction in nuclear staining intensity and more diffuse cell borders. Long-term experiments on NCIh295-xenografts revealed highest and sustained anti-tumoral effects for LEDP-M. Beside significant differences in tumor sizes between controls and LEDP-M we detected beginning from day 35 (p˂0.05) up to day 53 (p˂0.001), when the experiment was finished, highly significant reduced tumor sizes for LEDP-M compared with EDP-M. In summary, liposomal chemotherapeutic substances could represent a promising approach that would deserve testing in appropriate clinical protocols for treatment of patients with ACC.

Nothing to Disclose: CH, SJ, TM, MR, FB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by the Wilhelm-Sander-Stiftung (2011.003.1) to F.B. and C.H. Furthermore, research leading to these results has received funding from the seventh framework programme (FP7/2007-2013) under grant agreement number 259735. In addition, drugs have been received from Teni Boulikas regulon Inc and HRA Pharma and financial contribution has been provided by HRA Pharma.
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