Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel
| Autor: | Patrick Soon-Shiong, Vuong Trieu, Leslie Louie, Sherry Ci, Neil Desai, Andrew Yang, Bridget Beals, Rosie Yao, Chunlin Tao, Elizabeth Labao, Zhiwen Yao, Tapas De, Patricia E. Noker, Donald J. Dykes, Michael M. Hawkins |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research Time Factors Paclitaxel Endothelium Mice Nude Antineoplastic Agents Pharmacology Binding Competitive Polyethylene Glycols Mice chemistry.chemical_compound Albumins Cell Line Tumor Animals Humans Doubling time Medicine cardiovascular diseases Cells Cultured Dose-Response Relationship Drug business.industry Area under the curve Albumin Biological Transport Neoplasms Experimental Xenograft Model Antitumor Assays Survival Rate body regions Endothelial stem cell Dose–response relationship medicine.anatomical_structure Oncology Transcytosis chemistry Female Endothelium Vascular Albumin-Bound Paclitaxel business HT29 Cells |
| Zdroj: | Clinical Cancer Research. 12:1317-1324 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | ABI-007, an albumin-bound, 130-nm particle form of paclitaxel, was developed to avoid Cremophor/ethanol-associated toxicities in Cremophor-based paclitaxel (Taxol) and to exploit albumin receptor-mediated endothelial transport. We studied the antitumor activity, intratumoral paclitaxel accumulation, and endothelial transport for ABI-007 and Cremophor-based paclitaxel. Antitumor activity and mortality were assessed in nude mice bearing human tumor xenografts [lung (H522), breast (MX-1), ovarian (SK-OV-3), prostate (PC-3), and colon (HT29)] treated with ABI-007 or Cremophor-based paclitaxel. Intratumoral paclitaxel concentrations (MX-1-tumored mice) were compared for radiolabeled ABI-007 and Cremophor-based paclitaxel. In vitro endothelial transcytosis and Cremophor inhibition of paclitaxel binding to cells and albumin was compared for ABI-007 and Cremophor-based paclitaxel. Both ABI-007 and Cremophor-based paclitaxel caused tumor regression and prolonged survival; the order of sensitivity was lung > breast congruent with ovary > prostate > colon. The LD(50) and maximum tolerated dose for ABI-007 and Cremophor-based paclitaxel were 47 and 30 mg/kg/d and 30 and 13.4 mg/kg/d, respectively. At equitoxic dose, the ABI-007-treated groups showed more complete regressions, longer time to recurrence, longer doubling time, and prolonged survival. At equal dose, tumor paclitaxel area under the curve was 33% higher for ABI-007 versus Cremophor-based paclitaxel, indicating more effective intratumoral accumulation of ABI-007. Endothelial binding and transcytosis of paclitaxel were markedly higher for ABI-007 versus Cremophor-based paclitaxel, and this difference was abrogated by a known inhibitor of endothelial gp60 receptor/caveolar transport. In addition, Cremophor was found to inhibit binding of paclitaxel to endothelial cells and albumin. Enhanced endothelial cell binding and transcytosis for ABI-007 and inhibition by Cremophor in Cremophor-based paclitaxel may account in part for the greater efficacy and intratumor delivery of ABI-007. |
| Databáze: | OpenAIRE |
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