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Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer.

Publication ,  Journal Article
Previs, RA; Armaiz-Pena, GN; Lin, YG; Davis, AN; Pradeep, S; Dalton, HJ; Hansen, JM; Merritt, WM; Nick, AM; Langley, RR; Coleman, RL; Sood, AK
Published in: Mol Cancer Ther
December 2015

There is growing recognition of the important role of metronomic chemotherapy in cancer treatment. On the basis of their unique antiangiogenic effects, we tested the efficacy of nab-paclitaxel, which stimulates thrombospondin-1, and topotecan, which inhibits hypoxia-inducible factor 1-α, at metronomic dosing for the treatment of ovarian carcinoma. In vitro and in vivo SKOV3ip1, HeyA8, and HeyA8-MDR (taxane-resistant) orthotopic models were used to examine the effects of metronomic nab-paclitaxel and metronomic topotecan. We examined cell proliferation (Ki-67), apoptosis (cleaved caspase-3), and angiogenesis (microvessel density, MVD) in tumors obtained at necropsy. In vivo therapy experiments demonstrated treatment with metronomic nab-paclitaxel alone and in combination with metronomic topotecan resulted in significant reductions in tumor weight (62% in the SKOV3ip1 model, P < 0.01 and 96% in the HeyA8 model, P < 0.03) compared with vehicle (P < 0.01). In the HeyA8-MDR model, metronomic monotherapy with either cytotoxic agent had modest effects on tumor growth, but combination therapy decreased tumor burden by 61% compared with vehicle (P < 0.03). The greatest reduction in MVD (P < 0.05) and proliferation was seen in combination metronomic therapy groups. Combination metronomic therapy resulted in prolonged overall survival in vivo compared with other groups (P < 0.001). Tube formation was significantly inhibited in RF-24 endothelial cells exposed to media conditioned with metronomic nab-paclitaxel alone and media conditioned with combination metronomic nab-paclitaxel and metronomic topotecan. The combination of metronomic nab-paclitaxel and metronomic topotecan offers a novel, highly effective therapeutic approach for ovarian carcinoma that merits further clinical development.

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Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

December 2015

Volume

14

Issue

12

Start / End Page

2677 / 2686

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Topotecan
  • Paclitaxel
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Mice
  • Humans
  • Female
  • Drug Resistance, Neoplasm
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Previs, R. A., Armaiz-Pena, G. N., Lin, Y. G., Davis, A. N., Pradeep, S., Dalton, H. J., … Sood, A. K. (2015). Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer. Mol Cancer Ther, 14(12), 2677–2686. https://doi.org/10.1158/1535-7163.MCT-14-0630
Previs, Rebecca A., Guillermo N. Armaiz-Pena, Yvonne G. Lin, Ashley N. Davis, Sunila Pradeep, Heather J. Dalton, Jean M. Hansen, et al. “Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer.Mol Cancer Ther 14, no. 12 (December 2015): 2677–86. https://doi.org/10.1158/1535-7163.MCT-14-0630.
Previs RA, Armaiz-Pena GN, Lin YG, Davis AN, Pradeep S, Dalton HJ, et al. Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer. Mol Cancer Ther. 2015 Dec;14(12):2677–86.
Previs, Rebecca A., et al. “Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer.Mol Cancer Ther, vol. 14, no. 12, Dec. 2015, pp. 2677–86. Pubmed, doi:10.1158/1535-7163.MCT-14-0630.
Previs RA, Armaiz-Pena GN, Lin YG, Davis AN, Pradeep S, Dalton HJ, Hansen JM, Merritt WM, Nick AM, Langley RR, Coleman RL, Sood AK. Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer. Mol Cancer Ther. 2015 Dec;14(12):2677–2686.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

December 2015

Volume

14

Issue

12

Start / End Page

2677 / 2686

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Topotecan
  • Paclitaxel
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Mice
  • Humans
  • Female
  • Drug Resistance, Neoplasm