Jane S. Ricciuti, RPh, MS


February 07, 2005

In This Article

Antineoplastic Agents

Manufacturer: American Biosciences, Inc.

Drug Approval Classification: Original New Drug Application (Approval Date: 1/07/05)

Indication: Abraxane (paclitaxel protein-bound particles for injectable suspension) is 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 unless clinically contraindicated.

Dosing: The recommended regimen for Abraxane for injection is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.

Clinical Summary: Abraxane is an albumin-bound form of paclitaxel. Abraxane is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions.

Abraxane was studied in 2 single-arm, open-label studies and one randomized comparative study in 106 patients with metastatic breast cancer. Doses of 175 mg/m2 and 300 mg/m2 were used in clinical studies. Abraxane was compared to unbound paclitaxel, where the response rate was 21.5% in the Abraxane -treated groups compared with 11.1% in the paclitaxel-treated groups.

Adverse Effects: Patients treated with Abraxane 260 mg/m2 had a similar profile and incidence of adverse events to that of patients treated with paclitaxel 175 mg/m2 in the randomized trial. The most common adverse events were alopecia (90%), neutropenia (80%), sensory neuropathy (71%), abnormal ECG (60%), asthenia (47%), myalgia (44%), anemia (33%), hepatic AST elevations (39%), hepatic alkaline phosphatase elevations (36%), and nausea (30%). Myelosuppression and sensory neuropathy were dose related.

Pharmacokinetics: Paclitaxel pharmacokinetics following 30- and 180-minute infusions of Abraxane dose levels of 80-375 mg/m2 were studied. Following intravenous administration of Abraxane , paclitaxel plasma concentrations declined in a biphasic manner, the initial rapid decline representing distribution to the peripheral compartment and the slower second phase representing drug elimination. The terminal half-life was about 27 hours. The drug exposure (AUCs) was dose proportional over 80 to 375 mg/m2 and the pharmacokinetics of paclitaxel for Abraxane were independent of the duration of administration. At the recommended Abraxane clinical dose, 260 mg/m2, the mean maximum concentration of paclitaxel, which occurred at the end of the infusion, was 18,741 ng/mL. The mean total clearance was 15 L/hr/m2. The mean volume of distribution was 632 L/m2; the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of paclitaxel.


Abraxane (paclitaxel protein-bound particles) Injection Labeling