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Comparative benefits of Nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer

Awasthi, Niranjan ; Zhang, Changhua ; Schwarz, Anna M ; Hinz, Stefan ; Wang, Changguang ; Williams, Noelle S ; Schwarz, Margaret A ; Schwarz, Roderich E

Carcinogenesis (New York), 2013-10, Vol.34 (10), p.2361-2369 [Periódico revisado por pares]

England: Oxford University Press

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Comparative benefits of Nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer
Autor: Awasthi, Niranjan ; Zhang, Changhua ; Schwarz, Anna M ; Hinz, Stefan ; Wang, Changguang ; Williams, Noelle S ; Schwarz, Margaret A ; Schwarz, Roderich E
Assuntos: Albumin-Bound Paclitaxel ; Albumins - administration & dosage ; Albumins - pharmacology ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; Apoptosis - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Deoxycytidine - pharmacology ; Disease Models, Animal ; Docetaxel ; Female ; Humans ; Inhibitory Concentration 50 ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - mortality ; Neoplasms, Experimental - pathology ; Original Manuscript ; Paclitaxel - administration & dosage ; Paclitaxel - pharmacology ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Stathmin - metabolism ; Stromal Cells - drug effects ; Taxoids - administration & dosage ; Taxoids - pharmacology ; Tubulin - metabolism ; Tumor Burden - drug effects ; Xenograft Model Antitumor Assays
É parte de: Carcinogenesis (New York), 2013-10, Vol.34 (10), p.2361-2369
Descrição: Gemcitabine has limited clinical benefits in pancreatic ductal adenocarcinoma. The solvent-based traditional taxanes docetaxel and paclitaxel have not shown clinical results superior to gemcitabine. Nab-paclitaxel, a water-soluble albumin-bound paclitaxel, may carry superior distribution properties into the tumor microenvironment and has shown efficacy in multiple tumor types. We evaluated nab-paclitaxel effects compared with gemcitabine or docetaxel. For pancreatic ductal adenocarcinoma cells AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1, gemcitabine IC50 ranged from 494nM to 23.9 μM; docetaxel IC50 range was from 5 to 34nM; nab-paclitaxel IC50 range was from 243nM to 4.9 μM. Addition of IC25 dose of docetaxel or nab-paclitaxel decreased gemcitabine IC50. Net tumor growth inhibition after gemcitabine, docetaxel or nab-paclitaxel was 67, 31 and 72%, which corresponded with intratumoral proliferative and apoptotic indices. Tumor stromal density was decreased by nab-paclitaxel and to a lesser extent by docetaxel as measured through reduction in α-smooth muscle actin, S100A4 and collagen 1 expression. Animal survival was prolonged after nab-paclitaxel treatment (41 days, P < 0.002) compared with gemcitabine (32 days, P = 0.005), docetaxel (32 days, P = 0.005) and controls (20 days). Survival in nab-paclitaxel/gemcitabine and docetaxel/gemcitabine sequential treatment groups was not superior to nab-paclitaxel alone. Low-dose combination of gemcitabine with nab-paclitaxel or docetaxel was more effective compared with controls or gemcitabine alone but not superior to regular dose nab-paclitaxel alone. Combination treatment of gemcitabine+nab-paclitaxel or gemcitabine+docetaxel increased gemcitabine concentration in plasma and tumor. The superior antitumor activity of nab-paclitaxel provides a strong rationale for considering nab-paclitaxel as first-line monotherapy in pancreatic ductal adenocarcinoma.
Editor: England: Oxford University Press
Idioma: Inglês

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Comparative benefits of Nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer

Awasthi, Niranjan ; Zhang, Changhua ; Schwarz, Anna M ; Hinz, Stefan ; Wang, Changguang ; Williams, Noelle S ; Schwarz, Margaret A ; Schwarz, Roderich E

England: Oxford University Press

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