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Randomized Crossover Pharmacokinetic Study of Solvent-Based Paclitaxel and nab-Paclitaxel

Authors' Affiliations: ¹ Clinical Pharmacology Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland; ² Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; and ³ Abraxis BioScience, Inc., Los Angeles, California

Requests for reprints: William D. Figg, Medical Oncology Branch, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892. Phone: 301-402-3622; Fax: 301-402-8606; E-mail: wdfigg{at}helix.nih.gov.

Purpose: Abraxane (ABI-007) is a 130-nm albumin-bound (nab) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug.

Patients and Methods: Patients with malignant solid tumors were randomized to receive the recommended single-agent dose of nab-paclitaxel (260 mg/m² as a 30-minute infusion) or sb-paclitaxel (175 mg/m² as a 3-hour infusion). After cycle 1, patients crossed over to the alternate treatment. Pharmacokinetic studies were carried out for the first cycle of sb-paclitaxel and the first two cycles of nab-paclitaxel.

Results: Seventeen patients were treated, with 14 receiving at least one cycle each of nab-paclitaxel and sb-paclitaxel. No change in nab-paclitaxel pharmacokinetics was found between the first and second cycles (P = 0.95), suggesting limited intrasubject variability. Total drug exposure was comparable between the two formulations (P = 0.55) despite the dose difference. However, exposure to unbound paclitaxel was significantly higher after nab-paclitaxel administration, due to the increased free fraction (0.063 ± 0.021 versus 0.024 ± 0.009; P < 0.001).

Conclusion: This study shows that paclitaxel disposition is subject to considerable variability depending on the formulation used. Because systemic exposure to unbound paclitaxel is likely a driving force behind tumoral uptake, these findings explain, at least in part, previous observations that the administration of nab-paclitaxel is associated with augmented antitumor efficacy compared with solvent-based paclitaxel.