Albumin-bound paclitaxel: a next-generation taxane.
Taxanes are standard treatment for metastatic breast cancer; however, the solvents used as vehicles in these formulations cause severe toxicities. The FDA recently approved a solvent-free formulation of paclitaxel for the treatment of metastatic breast cancer that utilises 130-nanometer albumin-bound (nab) technology (Abraxane; nab-paclitaxel) to circumvent the requirement for solvents. nab-Paclitaxel utilises the natural properties of albumin to reversibly bind paclitaxel, transport it across the endothelial cell and concentrate it in areas of tumour. The proposed mechanism of drug delivery involves, in part, glycoprotein 60-mediated endothelial cell transcytosis of paclitaxel-bound albumin and accumulation in the area of tumour by albumin binding to SPARC (secreted protein, acidic and rich in cysteine). Clinical studies have shown that nab-paclitaxel is significantly more effective than paclitaxel formulated as Cremophor EL (CrEL, Taxol, CrEL-paclitaxel), with almost double the response rate, increased time to disease progression and increased survival in second-line patients. The absence of CrEL from the formulation is associated with decreased neutropenia and rapid improvement of peripheral neuropathy with nab-paclitaxel, compared with CrEL-paclitaxel. For these reasons, nab-paclitaxel can be administered using higher doses of paclitaxel than that achievable with CrEL-paclitaxel, with shorter infusion duration and without the requirement for corticosteroid and antihistamine premedication to reduce the risk of solvent-mediated hypersensitivity reactions. Taken together, these studies have demonstrated that nab technology has increased the therapeutic index of paclitaxel compared with the conventional, solvent-based formulation.
Gradishar
William J
WJ
Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. w-gradishar@northwestern.edu
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D007261:Infusions, Intra-Arterial; D036103:Nanotechnology; D009362:Neoplasm Metastasis; D015676:Osteonectin / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012997:Solvents / Q000633:toxicity; D015996:Survival Rate; D013810:Therapeutic Equivalency
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D015676:Osteonectin; D012997:Solvents; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol