Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel

Erin R. Gardner, William L. Dahut, Charity D. Scripture, Jacquin Jones, Jeanny B. Aragon-Ching, Neil Desai, Michael J. Hawkins, Alex Sparreboom, William D. Figg

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198 Scopus citations

Abstract

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 nabpaclitaxel 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.

Original languageEnglish
Pages (from-to)4200-4205
Number of pages6
JournalClinical Cancer Research
Volume14
Issue number13
DOIs
StatePublished - 1 Jul 2008
Externally publishedYes

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