nab-Paclitaxel (Albumin-Bound Microtubule Inhibitor)

Proposed Mechanism of Action

The taxanes act by inhibiting microtubule dynamics during cell division.1-6 The pharmacology of paclitaxel is dependent on its delivery vehicle, and various formulations have produced clinically different outcomes.7,8 nab-Paclitaxel uses albumin to deliver paclitaxel.1,2 Albumin is a ubiquitous carrier of biomolecules in the blood, and it may be consumed by growing tumors as a source of nutrients.9-12

nab-Paclitaxel by Disease State

nab-Paclitaxel in Pancreatic Cancer

  • Post Approval Research Pancreatic Cancer Pancreatic: Metastatic (first-line)
  • Phase 3 Pancreatic Cancer Pancreatic: Adjuvant

Rationale for Clinical Development

Preclinical studies in 2 different pancreatic cancer mouse models (mice with human pancreatic cancer xenografts and genetically engineered mice) demonstrated greater anti-tumor activity with nab-paclitaxel plus gemcitabine than with either agent alone.13,14 In each model, administration of nab-paclitaxel increased the intratumoral accumulation of gemcitabine. The investigators who used the xenograft model proposed that nab-paclitaxel accomplished this by disrupting the tumor stroma,13 and the investigators who used the genetic model suggested that the effect was caused by nab-paclitaxel leading to destabilization of a gemcitabine-metabolizing enzyme.14

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

References

  1. Abraxane for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) [package insert]. Summit, NJ: Celgene Corporation; 2014.
  2. Abraxane for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) [summary of product characteristics]. Uxbridge, UK: Celgene Europe Limited; 2013.
  3. Taxol (paclitaxel) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2011.
  4. Taxol (paclitaxel) [summary of product characteristics]. Utrecht, the Netherlands: Bristol-Myers Squibb BV; 2008.
  5. Taxotere (docetaxel) [package insert]. Bridgewater, NJ: sanofi-aventis US LLC; 2014.
  6. Taxotere (docetaxel) [summary of product characteristics]. Essex, UK: Aventis Pharma; 2013.
  7. Gardner ER, et al. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;862:213-218.
  8. Gradishar WJ, et al. J Clin Oncol. 2005;23:7794-7803.
  9. Peters T Jr. Adv Protein Chem. 1985;37:161-245.
  10. Kiessling F, et al. Invest Radiol. 2002;37:193-198.
  11. Kratz F. J Control Release. 2008;132:171-183.
  12. Kremer P, et al. Anticancer Drugs. 2002;13:615-623.
  13. Von Hoff DD, et al. J Clin Oncol. 2011;29:4548-4554.
  14. Frese KK, et al. Cancer Discov. 2012;2:260-269.