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

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

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Abstract

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 494 nM to 23.9μM; docetaxel IC50 range was from 5 to 34 nM; nabpaclitaxel IC50 range was from 243 nM to 4.9 μM. Addition of IC25 dose of docetaxel or nab-paclitaxel decreased gemcitabine IC50. Net tumor growth inhibition after gemcitabine, docetaxel or nabpaclitaxel 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 a-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.

Original languageEnglish (US)
Pages (from-to)2361-2369
Number of pages9
JournalCarcinogenesis
Volume34
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

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docetaxel
gemcitabine
Polysorbates
Pancreatic Neoplasms
Inhibitory Concentration 50
Adenocarcinoma
130-nm albumin-bound paclitaxel
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

Awasthi, N., Zhang, C., Schwarz, A. M., Hinz, S., Wang, C., Williams, N. S., ... Schwarz, R. E. (2013). Comparative benefits of nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer. Carcinogenesis, 34(10), 2361-2369. https://doi.org/10.1093/carcin/bgt227

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; Schwarz, Roderich E.

In: Carcinogenesis, Vol. 34, No. 10, 10.2013, p. 2361-2369.

Research output: Contribution to journalArticle

Awasthi, N, Zhang, C, Schwarz, AM, Hinz, S, Wang, C, Williams, NS, Schwarz, M & Schwarz, RE 2013, 'Comparative benefits of nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer', Carcinogenesis, vol. 34, no. 10, pp. 2361-2369. https://doi.org/10.1093/carcin/bgt227
Awasthi, Niranjan ; Zhang, Changhua ; Schwarz, Anna M. ; Hinz, Stefan ; Wang, Changguang ; Williams, Noelle S. ; Schwarz, Margaret ; Schwarz, Roderich E. / Comparative benefits of nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer. In: Carcinogenesis. 2013 ; Vol. 34, No. 10. pp. 2361-2369.
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