Nab-Paclitaxel (Abraxane)
From Standard of Care
An albumin-bound 130-nanometer particle form of paclitaxel.
Biologically interactive nanometer sized albumin bound paclitaxel particle developed to avoid polyethylated castor oil toxicity.
This drug was developed to avert toxicities associated with the Crewmophor vehicle used in solvent based paclitaxel, as it is solvent free and Cremophor EL free.
By using the transport properties of albumin, this agent overcomes the indissolubility of many chemotherapy drugs, eliminates solvent related toxicities and cuts and fusion time to 30 min. without premedication.
Crosses endothelial cell walls, and provides rapid tissue and intracellular availability.
Has a 33% higher accumulation of paclitaxel in tumors compared with solvent based paclitaxel at equal doses in tumor xenografts.
An anticancer agent that utilizes properties of albumin, which is a natural carrier of lipophilic molecules.
Nanoparticle albumin bound paclitaxel solvent free 130 nanometer particle formulation of paclitaxel.
Administered as a colloidal suspension which allows the safe infusion of higher doses of paclitaxel (than standard paclitaxel) with shorter infusion time of 30 minutes rather than 3 hours and no premedications.
Albumin bound paclitaxel mediates drug transport and demonstrates a 4.5 fold increases in drug transport across endothelial cells compared to standard paclitaxel.
Caveolin-1 mediates the active transport of albumin based molecules across the endothelium into tumors and is overexpressed in non-small cell lung cancer, and high expression is associated with metastases and poor prognosis.
Indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy: prior therapy should have included an anthracycline agent unless clinically contraindicated.
Maximum tolerated dose is 300 mg/m2, approximately 70% higher than conventional paclitaxel about 175 mg/m2.
Recommended regimen is 260 mg/m2 intravenously over 30 minutes every three weeks.
Not associated with severe hypersensitivity reactions.
Dose limiting toxicity include sensory neuropathy, stomatitis, and superficial keratopathy.
Response rate in metastatic breast cancer 64% for first-line patients with overall response rate of 48%. In a phase III study of albumin bound paclitaxel compared to solvent based paclitaxel in taxane naive metastatic breast cancer patients resulted in a 33% vs. 19% response rate with a longer time to tumor progression of 23 weeks vs. 16.9 weeks (Gradishar).
Increases expression of Secreted Protein And Rich in Cysteine (SPARC) correlates with improved response to this agent due to a SPARC-albumin interaction in pancreatic cancer. SPARC may play a role in selectively concentrating this agent in pancreatic cancer.
Consistently demonstrates superior efficacy compared to paclitaxel in clinical trials for metastatic breast cancer.
Indicated for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy.
This drug in metastatic breast cancer has a significantly higher overall response rate, significant longer time to progression, significant greater overall survival in patients treated with a second line or greater therapy compared with patients who receive paclitaxel (Gradishar WJ et al).
In a randomized study in first-line treatment for metastatic breast cancer nab-paclitaxel 150 mg meter squared weekly versus docetaxel 100 mg per meter squared Q3 weeks resulted in a statistically and clinically significant prolongation of progression free survival of greater than five months (Gradishar WJ et al).
Is indicated for the first-line treatment of locally advanced or metastatic Non–small cell carcinoma of the lung, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) trial of nab- paclitaxel plus gemcitabine: nab- paclitaxel 125/ m2 plus gemcitabine 1000 mg/m2 days 1,8 and 15 q4weeks or gemcitabine alone-median overall survival 8.5 vs 6.7 months, 1 Year survival 35% vs 22%, 1year progression free survival 5.5% vs 3.7%, and overall response rate 23% vs 7% (Von Hoff DD et al).
Injectable suspension.
Bone marrow suppression is dose dependent and the dose limiting toxicity.
