Endocrine Abstracts

Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane (M). Recently, we investigated together with M the effects of i) the classical EDP protocol (etoposide, doxorubicin, and cisplatin) and ii) a novel paclitaxel containing scheme PDP (paclitaxel, doxorubicin, and cisplatin) on human NCIh295 cells 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 called LEDP-M (etoposide, liposomal doxorubicin, and liposomal cisplatin) and LPDP-M (nab-paclitaxel, liposomal doxorubicin, and liposomal cisplatin). In short-term therapeutic experiments on NCIh295-xenografts EDP-M did not induce a significant loss of tumor cells while PDP-M (P<0.01), LEDP-M (P<0.01) and LPDP-M (P<0.01) resulted overall in significant tumor cell reduction 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 vs 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 compared with controls, while kidneys of EDP-M and PDP-M groups showed by trend reduced nuclear staining intensities 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 (end of experiment, P<0.001) highly significant reduced tumor sizes for LEDP-M compared with EDP-M. In summary, liposomal chemotherapies could represent promising approaches that would deserve testing in clinical protocols for patients with ACC.